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This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-R. Patients were evaluated at baseline and 30 days after the final treatment by corneometry and ultrasound strain elastography. At the final follow-up appointment (Day 30 (D30) for Group 1, Day 60 (D60) for Group 2), both the investigator and the patient assessed outcome efficacy using the 5-point Global Aesthetic Improvement Scale (GAIS) and the Pain and Comfort Visual Analogue Scales (VAS). A total of 40 patients were included in the final analysis; mean age was 41.7 years (range: 25-60), 85.0% were female (n = 34/40), and most patients had mild rosacea, acne-prone, or dry skin. Of the 40 patients, 6 (16.0%) exhibited mild rosacea, and 12 (30.0%) had acne-prone skin. No patients withdrew from the study. Hydration levels, as assessed by corneometry, significantly improved following treatment with CPM-R by an average of 14.9% after a single treatment and 16.6% after two treatments spaced four weeks apart (p < 0.001). The investigator and patient evaluations of facial appearance were either "much improved" or "very much improved" in all patients who underwent a single-treatment or two-treatment protocol. No serious adverse events were reported. Minor and transient side effects (e.g., local mild erythema and ecchymosis) were reported in 15.0% (n = 6/40) and 7.5% (n = 3/40) of cases, respectively, and resolved spontaneously within 24-72 h. Patients reported minimal discomfort, with 75.0% (n = 30/40) of the patients reporting an average VAS pain score of 1 (out of 10). This study demonstrated that the use of CPM-R delivered through retro-linear and fanning techniques with a microcannula is an innovative, effective, safe, an

Background: Rosacea is a chronic facial skin disease in which persistent erythema is a significant clinical problem, often resistant to standard therapies. Intensive pulsating light (IPL) has become a recognised and effective method of treating erythema and telangiectasia. The latest recommendations emphasise the advantage of combining subjective clinical assessments with objective imaging analyses in monitoring therapy effects. Methods: A total of 20 patients with rosacea qualified for this study. They were subjected to three polychromatic light procedures (Lumecca, Inmode; wavelength of 515-1200 nm) at 21-day intervals. The skin condition was documented photographically, and the degree of erythema was assessed on the basis of the Clinician Erythema Assessment (CEA) scale and objective analysis of the skin texture, using the parameters of contrast and homogeneity of the grey level co-occurrence matrix (GLCM). Results: A series of three polychromatic light treatments yielded a significant clinical improvement in all patients. The mean CEA value decreased by 61.11%, whereas the GLCM contrast in all the analysed facial areas dropped by about 17%, and homogeneity increased by 4-5%. The effects persisted for at least three months after the treatments. A high correlation of CEA scale results with GLCM parameters (R = 0.81-0.94 for contrast; R = -0.77 to -0.83 for homogeneity) was observed. Conclusions: Three polychromatic light treatments proved to be a very effective method of reducing erythema in rosacea, confirmed by both clinical evaluation and objective imaging analysis. The effects of therapy were durable and clear. Integration of the subjective method (CEA) with GLCM analysis can be a path for future research and clinical practice in the assessment of erythematous skin lesions. Background/Objectives: "Ozempic face" is an aesthetic side effect associated with the use of the antidiabetic agent Ozempic (semaglutide), characterized by a prematurely aged and fatigued facial appearance due to rapid weight loss. Currently, treatment options for this condition are limited. In this study, we present our clinical experience with the BodyTite device, provided by InMode Italy S.r.l. (Rome, Italy). Materials and Methods: We report a case series involving 24 patients (19 women and 5 men, aged 27-65 years), treated with subdermal bipolar radiofrequency (Endotissutal Bipolar Radiofrequency) between 2023 and 2024. All patients underwent a minimum follow-up of 12 months. At the end of the follow-up period, patients rated their satisfaction on a from 0 to 10 scale, and an independent expert assessed the stability of clinical outcomes. Results: The majority of patients reported high satisfaction levels (≥8), which correlated with the independent expert's evaluation of treatment efficacy and result stability. The only observed adverse event was transient cutaneous erythema. Conclusions: "Ozempic face" is an increasingly common side effect associated with newer classes of antidiabetic medications. Although these drugs offer significant metabolic benefits, the accompanying facial volume loss and aging are often poorly tolerated by patients. Our findings suggest that subdermal bipolar radiofrequency represents a safe, low-risk, and cost-effective therapeutic option for the aesthetic management of Ozempic face. Autonomic nerves and ganglia that affect bladder sensation and detrusor contractility are present below the proximal urethra and trigone. Radiofrequency energy has been shown to potentially ablate/modulate these nerves in overactive bladder (OAB) patients. In this study, we intended to establish the safety and efficacy of transvaginal radiofrequency energy delivered via a vaginal Morpheus (Inmode) microneedling device in female patients with OAB. Women with known OAB, both primary and refractory as well as urge-predominant mixed urinary incontinence, were treated in the office setting using transvaginal detrusor nerve radiofrequency ablation to a depth of 7 mm.The primary outcome was the change in urge incontinence episodes on a 3-day voiding diary at 3 months after procedure. Secondary outcomes were the following at 1 and 3 months: the change in urinary frequency and incontinence, Incontinence Impact Questionnaire-7 (IIQ-7), Urinary Distress Inventory-6 (UDI-6), and Patient's Perception of Bladder Condition (PPBC). A pain assessment was collected immediately after the procedure and a Patient Global Impression of Improvement questionnaire was collected at 3 months. From 07/2023 to 02/2024, 32 were enrolled and 31 were followed for 3 months after treatment. Episodes of urgency incontinence, IIQ-7, UDI-6, PPBC, urinary frequency, and episodes of severe urinary urgency, had statistically significant improvement. Significant Analysis of Variance (ANOVA) testing ( P  < 0.001) was encountered with the IIQ-7, UDI-6, PPBC, urinary frequency, and urgency incontinence. No adverse events were encountered. Across all outcome metrics, the transvaginal detrusor nerve radiofrequency ablation for treatment of overactive bladder showed statistically significant improvements. Background: The techniques of choice used in the treatment of extensive vascular lesions of the face are methods based on high-energy light sources, such as lasers and IPL (intense pulsed light). The techniques commonly employed to detect blood vessel abnormalities in skin primarily rely on semi-quantitative or qualitative scales. Methods: The study was conducted on a group of 38 volunteers; a series of three treatments was performed using an IPL source (Lumecca, Inmode, Israel). The vessels' response to the high-energy light was verified using the following quantitative methods: mexametric measurements, hyperspectral imaging, and directional reflectance measurements. Results: In the mexameter measurement, statistically non-significant differences were obtained in the hemoglobin content in the skin condition prior to and following multiple intense pulsed light sessions. Studies performed using a hyperspectral camera showed that at a wavelength of 580 nm, the increase in skin reflectance after the treatment was statistically significant. Total directional reflectance measurements showed that at wavelengths of 400-540 nm and 480-600 nm, following the IPL treatment, the skin reflectance increased statistically significantly. Implementing three consecutive intense pulsed light procedures appears adequate to obtain a clinically satisfactory reduction in vascular changes in the facial skin. Mexametric measurements do not enable the assessment of the reaction of blood vessels to IPL. Conclusions: Hyperspectral imaging is an effective method for the quantitative assessment of skin vascular lesions. The best results in the assessment of vascular lesions using hyperspectral imaging are obtained at wavelengths of 420 nm and 580 nm. The hemispheric directional reflectance method allows for a quick, accurate, and repeatable assessment of vascular skin changes. Surgeons and providers in aesthetic medicine seek noninvasive devices that can be utilized for safe, efficient, and effective body contouring. Patient demand has propelled the development of novel devices that can simultaneously improve skin laxity, adipolysis along with stimulation of muscle hypertrophy. To determine the efficacy of body contouring after 3 treatments using the noninvasive Transform (InMode, Lake Forest, CA) device. A prospective, multicenter study was performed. Outcomes evaluated include: standardized caliper and ultrasound measurements of abdominal skin/soft-tissue thickness, waist circumference, histologic evaluation, patient comfort, and satisfaction assessments. Forty-four patients were successfully enrolled in the study and completed the series of 3 treatments which involved combined electrical muscle stimulation (EMS) and noninvasive bipolar radiofrequency (RF). Abdominal ultrasound measurements reveal a

Hidradenitis suppurativa (HS) remains a therapeutically challenging disease despite expanding research and evolving systemic treatments. Energy-based modalities, such as fractional microneedling radiofrequency (FMR), are being increasingly explored as novel treatment options. To evaluate the real-world efficacy and safety of Morpheus8-based FMR treatment in patients with HS. This retrospective analysis included 25 HS patients treated at a tertiary dermatology center. Seventeen patients who completed ≥ 2 FMR sessions were included in the efficacy analysis. Outcomes were assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4) and IHS4-55 (≥ 55% reduction). High-frequency ultrasound (HFUS) was used in selected cases to assess treatment response and inflammatory changes. Sixteen of the 17 patients (94.1%) evaluated for efficacy showed clinical improvement, and nine (52.9%) achieved an IHS4-55 response. The mean IHS4 reduction was 4.6 ± 2.5. The highest response rates were observed in the face, chest, and gluteal regions, while groin and thigh showed the lowest. HFUS confirmed a reduction in inflammation. Treatment was generally well tolerated, with pain cited as the most common reason for discontinuation in 3 of 25 patients (12%). FMR appears to be a safe and effective treatment option for patients with moderate-to-severe HS, including those with refractory disease and lesions in anatomically challenging areas. Clinical outcomes in our cohort were comparable to those reported for advanced systemic agents and other technology-based interventions. These findings support FMR's potential role in personalized HS management - either as a standalone intervention or in combination with systemic or procedural treatments. This study evaluated a novel approach combining low-energy Morpheus8 radiofrequency (RF) microneedling and nanofat grafting for facial rejuvenation, aiming to preserve adipose tissue while enhancing skin quality. A retrospective analysis was conducted on 20 patients (aged 20-45 y) treated with nanofat injections immediately after low-energy RF microneedling. Outcomes included Global Aesthetic Improvement Scale scores and nonsurgical parameters (pore visibility, skin luminosity, and fine wrinkles), assessed at 1, 3, and 12 months posttreatment. Pretreatment Global Aesthetic Improvement Scale scores (mean = 3.35, SD = 0.61) showed significant improvement posttreatment (mean = 1.76, SD = 0.87; P < 0.001). Sustained enhancement was observed at 3 months (mean = 1.52, SD = 0.63; P < 0.001), with 85% of patients rated as "very much improved." Blinded evaluations confirmed visible reductions in pore visibility, increased skin luminosity, and diminished fine wrinkles in nonsurgical regions (malar, perioral). No adverse events were reported. The combination of low-energy RF microneedling and nanofat grafting synergistically improves facial aesthetics by targeting regenerative and structural aging markers. Specific enhancements in nonsurgical regions underscore the value of this adjunctive approach. Larger controlled studies are warranted to establish causality. In his practice, the author has been using noninvasive devices, including Evolve X-radiofrequency-based procedure for tightening of the skin, melting of the subdermal fat deposits and muscle stimulation, all done simultaneously together and truSculpt flex-electrical muscle stimulation. Minimally invasive procedures include BodyTite, FaceTite, and AccuTite, radiofrequency-based procedures for permanent fat destruction and tightening of the skin. Morpheus8 and Morpheus8 Body are radiofrequency based-procedures for tightening of the skin. VASERlipo is an ultrasound-based procedure for liposuction and muscle definition. Vibrational type of liposuction has been used for the purpose of liposuction and muscle definition in combination with VASERlipo. A subset of facelift patients have premature redevelopment of skin laxity in the lower face and neck. Many patients seek alternatives to revision facelifts to avoid high risks and costs. Radiofrequency-assisted lipolysis (RFAL) with Radiofrequency (RF) microneedling may be alternative minimally invasive options. To evaluate the efficacy of radiofrequency energy devices for treatment of premature jowl and neck skin laxity following facialplasty. This is a single-center, prospective study of patients seeking treatment for jowl and neck skin laxity 1-5 years following facialplasty. Treatment was performed with the InMode radiofrequency AccuTite® and Morpheus8® systems. Study duration was 12 months with 6 months of follow-up. Endpoints included improvement in skin tightening assessed by blinded investigators, and investigator and subject assessment of skin appearance. Subjects also rated satisfaction with treatment and pain levels. The study protocol was completed by nine patients. Based on investigator evaluations, 33% had marked improvement at 3 months, which increased to 55% at 6-month postprocedure. Patient-reported improvement was "markedly improved" in 67%, "moderate improvement" in 11%, and "slight improvement" in 22% at 3 months. Overall patient satisfaction was rated as "very satisfied" by 33% and "satisfied" by 67% at 3 months. There were no adverse events reported. The results of this study provide supporting evidence that RFAL technology can provide a safe, minimally invasive, and effective treatment for skin laxity in the jowls and neck in patients who desire further correction after undergoing primary facelift.

Skin laxity and static wrinkles cause aesthetic concerns. Monopolar radiofrequency (RF) could produce measurable improvement. This study aims to evaluate the efficacy and safety of a novel monopolar RF device, YOUMAGIC, for skin tightening and rejuvenation treatment. In this multicenter, 6-month, assessor blind, positive parallel-controlled study, subjects were randomized to receive a single treatment with YOUMAGIC or Thermage (CPT; Solta Medical). Efficacy was mainly determined by the effective rate of facial wrinkle improvement [Global Aesthetic Improvement Scale (GAIS)] 90 days after treatment. Safety assessments were conducted through structured inquiries, adverse event diaries maintained by subjects, laboratory tests, and monitoring of vital signs. Of the 230 enrolled subjects, 212 were included in the final analysis. The proportions of subjects who achieved ≤ 3-grade on the GAIS were 100% in the treatment group and 98.10% in the control group 90 days after treatment. No significant differences were found between the treatment and control groups. No subjects experienced any serious adverse events. In conclusion, the novel monopolar RF device YOUMAGIC is clinically safe and effective for skin tightening and is not inferior to the regular RF therapeutic device. Clinical trial registry identifier: ChiCTR2400087993. URL: https://www.chictr.org.cn/showproj.html?proj=225518 2024-08-08 retrospectively registered. The online version contains supplementary material available at 10.1007/s10103-026-04841-4. To evaluate the efficacy and safety of a novel monopolar RF device for skin tightening and rejuvenation treatment. Forty participants were enrolled in the study. Subjects randomized to the treatment group received a single treatment with the novel RF device (YOUMAGIC), whereas the control group received regular RF treatment (Thermage CPT; Solta Medical). Digital photographs and Antera 3D photographs were taken at baseline, 1-, 3-, and 6-month posttreatment. The depression volume of nasolabial folds (NLFs) in each visit was evaluated using the Antera 3D imaging program. The pain was evaluated by pain measurement scales immediately after treatment. Any procedure-related side effects were documented and examined. Posttreatment results were compared with the baseline; statistically significant mean depression volume (MDV) changes of NLFs were found at 1, 3, and 6 months posttreatment. No significant MDV changes were found between the treatment and control groups. No severe adverse events were reported. Our study demonstrates that the novel monopolar RF device is clinically safe and effective for skin tightening in the lower face area, and is not inferior to the regular RF therapeutic device. The aim of this questionnaire-based study was to measure the level of appreciation, practice patterns, and side effects of monopolar radiofrequency treatment among Korean dermatologists practicing the most updated monopolar radiofrequency device (Thermage FLX, Thermage Inc., Hayward, California). According to a total of 52 surveys analyzed, this latest device (Thermage FLX) was considered more effective (57.4%), faster with reduced treatment time (66.0%), and more painful (25.5%) compared with Thermage CPT. Asians in their 40s were considered to benefit most and skin thickness continued to be the most important determinant in terms of responsiveness to Thermage FLX. The interval between treatments was mainly 1 year (51.9%) with the 600 REP 4 cm2 new total tip being preferred by 86.5% of Thermage FLX users. The treatment energy and the complication rate of Thermage was lower than what we reported in 2017 and 2011 which is likely due to the optimized energy delivery of Thermage FLX and the subsequent gentle treatment. We hope our updated data enable dermatologists to better utilize monopolar radiofrequency in their practice. Nonablative procedures for facial rejuvenation have become increasingly popular. One such method to improve laxity and diminish rhytids is monopolar capacitively coupled radiofrequency (MRF). The authors discuss clinical studies using MRF. The authors also discuss their clinical experiences as well as recommendations for optimal results. MRF using the Thermage CPT system (Solta Medical, Hayward, California) offers minimal downtime with a favorable side-effect profile. Although there are many radiofrequency devices on the market for aesthetic use, MRF has the most clinical trials to date to support its use as an effective, evidence-based modality to improve rhytids and tighten the skin.

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

This study assessed participants' experience with their clinical trial and explored perceived health improvements to support quality improvement initiatives. A cross-sectional survey was conducted among participants of a randomized, double-blind clinical trial on magnesium supplementation in type 2 diabetes. All participants were invited to complete a 25-item survey after providing informed consent. The survey covered general information, core trial experience (Five-Point-Likert-Scale), symptom improvement, overall satisfaction, and open-ended questions. The tool was bilingually developed, culturally adapted, and psychometrically tested for consistency and validity. Both quantitative and qualitative thematic analysis were performed. The survey demonstrated a high internal consistency (Cronbach's alpha=0.93), and a strong construct validity characterized by a predominant unidimensional structure (Kaiser-Meyer-Olkin value=0.897). Of 227 contacted participants, 132 completed the survey (response rate: 58.15%). Satisfaction scores were consistently positive, especially for staff professionalism, respect for time, and informed consent clarity. Most respondents (75%) were willing to join future trials, and 87.88% would recommend participation. Over half reported symptom improvements, particularly in muscle cramps, energy, and sleep quality. No significant association was found between satisfaction and symptom improvement. Satisfaction was high across all educational levels. Open-ended responses emphasized staff professionalism, clear communication, and perceived health benefits as key factors to the overall reported satisfaction. Respondents reported a consistently high satisfaction level, with perceived symptom improvements and strong willingness to future participation. This internally reliable and structurally valid survey captured meaningful feedback and may serve as a valuable quality improvement initiative to enhance patient engagement and optimize trial conduct, however, within the study's limitations. To evaluate and compare the responses of ChatGPT and Google Gemini to common patient questions about scaphoid fracture and scaphoid nonunion, and to compare responses between hand fellowship-trained orthopedic and plastic surgeons. A list of 30 common patient questions about scaphoid fracture and nonunion was developed and classified using Norman Webb's Depth of Knowledge levels 1-4. Each question was input into ChatGPT-4o and Google Gemini 2.0 Flash. An evaluation guide was created with four domains for each response, each rated on a Likert scale from 1-5: accuracy, clarity, Artificial Intelligence Response Metric, and comparison to an in-person clinician interaction. Responses were evaluated by three orthopedic and three plastic hand surgeons. Statistical comparisons were performed using nonparametric tests to assess differences between AI platforms, domains, question complexity, and surgical specialty. There were no considerable differences between mean Likert scale scores for ChatGPT and Google Gemini. Plastic surgeons rated responses higher than orthopedic surgeons overall and for ChatGPT. Google Gemini performed better for DOK level 2 and level 3 questions. ChatGPT's responses had greater clarity. For both platforms, ratings for clinician comparability across all DOK levels were considerably lower than scores for all other metrics. Our findings suggest that ChatGPT and Google Gemini offer clinical use for patient care regarding scaphoid fracture and nonunion. However, clinician comparability was not a key strength for either platform, highlighting a key area for improvement for AI-based large language models in clinical application. Diagnostic V. Graduate employability is increasingly emphasized in higher education, yet how students from low-income families develop employability remains under-theorized, particularly regarding the interplay between psychological resources and contextual constraints. Using reflexive thematic analysis, we analyzed semi-structured interviews with 11 university students from low-income families to examine perceived influences and mechanisms underlying employability development. Nineteen sub-themes converged into four higher-order themes: psychological capital, resource-compensatory proactivity, goal clarity, and capability enactment. Self-efficacy and optimism energized proactive behaviors that sharpened career goals. Goal clarity then prompted deliberate practice that strengthened learning and self-management, resilience, and socio-communicative skills. These processes unfolded within family and university contexts, including economic constraint, prestige-based stratification, teachers' guidance, seniors' experience transfer, extracurricular participation, and internship and part-time work, which operated as filters or scaffolds. Mastery experiences further fed back to reinforce self-efficacy and optimism. The resulting conceptual model localizes Social Cognitive Career Theory to a low-socioeconomic-status setting and suggests that strengthening psychological resources and engineering opportunity structures are jointly necessary for translating motivation into demonstrable employability. This article introduces the Mind Locker Method, a lived-experience-based psychological method for sustaining resilience in individuals living with chronic pain, including trigeminal neuralgia (TN). Developed over a decade through lived experience with TN, the method integrates analytic autoethnography as methodology with clinical training and trauma-informed regulation strategies. The method consists of five structured pillars: self-awareness and body literacy, mental anchoring and redirection, breath and movement calibration, emotional containment, and adaptation through pain. These strategies are designed for real-time use during physical and emotional crises to preserve clarity, function, and autonomy. Unlike many traditional models that emphasize distraction or suppression, the Mind Locker Method engages pain directly as analytic material, offering a distinct neuroplastic and identity-preserving framework. To the best of current knowledge, this may be the first named psychological model for chronic pain authored by a Black woman psychologist with lived experience of TN. As such, it stands as both a practical toolkit and a feminist-epistemic intervention, reclaiming the authority of women of color to name theories in psychology. With the rising incidence of spinal disorders, demand for minimally invasive spinal surgery using endoscopes continues to grow, owing to advantages such as reduced blood loss, minimal trauma, and rapid recovery. As the core intraoperative imaging device, the clarity of endoscopic imaging directly impacts surgical outcomes. However, as a form of underwater minimally invasive surgery, spinal endoscopy frequently involves intraoperative bleeding. The strong absorption and multiple scattering caused by blood flow constitute a dynamic scattering medium interference, severely compromising imaging quality during surgery. This leads to difficulties in locating bleeding points and prolonged operative times. To mitigate the impact of intraoperative blood scattering media on endoscopic imaging quality, this paper proposes a spinal endoscopic blood scattering medium imaging method based on spatial similarity cross-correlation of light fields and deep learning. This method first performs fusion preprocessing on the multi-angle raw scattered subaperture images acquired via light field capture. Subsequently, the study conducts full-scale structural analysis on the blurred images captured by the light field camera. Building upon the existing U-Net network principle, the network architecture is enhanced to construct a full-scale U-Net network, which is employed to restore the pre-processed images. Ultimately, experiments validate the method's efficacy, using this method to restore images of blood scattering media transm

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are widely used for weight management and type 2 diabetes, but reports of reduced skin laxity and volume have raised aesthetic concerns. This study evaluates the first integrated skincare protocol designed for GLP-1 RA users. This 12-week, double-blind, randomized, split-face/split-neck study included 25 GLP-1 RA users (mean age 53.36 years) with mild-to-moderate skin aging, including male and female participants with Fitzpatrick skin types II to VI. All participants applied a topical regimen featuring Proxylane and wild fruit flavonoids (Flavo-Proxylane) to one side of the face/neck and a placebo to the other. After 4 weeks of topical monotherapy, participants received a single focused ultrasound treatment, followed by an additional 8 weeks of topical therapy. Outcomes included blinded image evaluation, 13 clinical grading parameters (via modified Griffiths scale), Global Aesthetic Improvement Scale scores, tolerability, and patient-reported satisfaction. All participants completed the study and lost an average of 3.7 lb. After 4 weeks of Flavo-Proxylane monotherapy, significant improvements were observed for facial skin laxity (- 16%; P < 0.001) and marionette lines (- 5%; P < 0.05), while no significant changes were observed with placebo. By week 12, the combined regimen achieved amplified improvements versus baseline, week 4, and placebo (all P < 0.001), with total reductions of 44% in skin laxity and 34% in marionette lines. Significant improvements were observed across all 13 clinical parameters. Overall improvement rating favored Flavo-Proxylane, with 94% reporting moderate-to-significant improvement versus 30% for placebo. Flavo-Proxylane treatment was well tolerated, with 84% reporting improved skin appearance and only three mild, self-resolving adverse events. This study demonstrates that an integrated regimen with Flavo-Proxylane products and ultrasound may improve aesthetic outcomes in a diverse range of participants undergoing GLP-1 RA treatment. Skin laxity, driven by collagen/elastin degradation and aging, is targeted by micro-focused ultrasound (MFU) through depth-specific thermal coagulation to induce collagen remodeling, yet parameter-dependent thermal kinetics and safety thresholds remain underexplored, limiting protocol optimization. To validate the dose-effect relationship of MFU using in vitro porcine skin tissues and evaluate its safety and efficacy for human facial skin tightening. Porcine skin tissues containing intact skin, fat, and muscle layers were treated with 8D-DL 3.0, 8D-DL 4.5, Vmax-DL 3.0, and Vmax-DL 4.5 handpieces. Subcutaneous temperatures at depths of 2.0 mm, 3.0 mm, 4.5 mm, and 6.0 mm were recorded under varying parameters (energy levels and exposure durations). Twenty patients undergoing single-session MFU facial treatment between June and August 2024 were enrolled. Skin tightening outcomes were assessed at 30- and 90-days post-treatment. For 8D-DL 3.0 and Vmax-DL 3.0 handpieces, peak temperatures occurred at 3.0 mm depth across all energy levels and exposure durations. For 8D-DL 4.5 and Vmax-DL 4.5 handpieces, peak temperatures localized at 4.5 mm. Focal depth temperatures increased significantly with higher energy levels and prolonged exposure. At 30- and 90-days post-treatment, upward displacement and volume reduction in bilateral cheek and jawline regions were observed. Mild procedural pain was reported, with no adverse events. MFU-induced thermal peaks align with preset focal depths, demonstrating parameter-dependent thermal accumulation. The procedure safely achieves clinically significant facial skin tightening. Transcranial focused ultrasound (tFUS) is an emerging noninvasive neuromodulation modality with the ability to target deep brain structures with high spatial precision. Despite its promise, rigorous evaluation of its efficacy is limited by the absence of reliable, fully double-blind sham methodologies. To develop and validate a pair of visually and mechanically indistinguishable acoustic coupling pads that enable true double-blind tFUS neuromodulation studies by providing either efficient ultrasound transmission or robust ultrasound blocking without altering participant or operator experience. Two coupling pads were engineered: a transmitting pad designed to allow <5% pressure amplitude loss relative to free-water propagation, and a non-transmitting pad designed to attenuate ultrasound by ≥40 dB. Both pads used a Dragon Skin 10 NV silicone base and were identical in size, appearance, flexibility, and handling. The non-transmitting pad incorporated an encapsulated air-based blocking layer using an open-cell polyethylene foam insert. Acoustic performance was evaluated in a water tank using a 650 kHz BrainSonix transducer and a calibrated needle hydrophone. Sound speed of the silicone material was measured using pulse-echo techniques. Twenty-three matched transmitting and non-transmitting pad pairs were fabricated and tested. Transmitting pads demonstrated a mean attenuation of -0.41 ± 0.53 dB, satisfying the design criterion of minimal acoustic loss. Non-transmitting pads demonstrated a mean attenuation of -48.61 ± 4.33 dB, exceeding the required -40 dB threshold for effective sham conditions. The Dragon Skin 10 NV substrate exhibited a sound speed of 964.72 m/s and produced <2 mm axial focal shift for standard pad thicknesses, with no measurable change in focal width. Both pad types were visually and tactually indistinguishable, could not be differentiated by experienced operators or participants, and maintained mechanical integrity after repeated cleaning. These acoustically engineered coupling pads provide a practical and validated solution for achieving true single- and double-blind conditions in tFUS neuromodulation studies. By preserving identical sensory and procedural experiences while enabling precise control over ultrasound transmission, this approach addresses a critical methodological gap in human ultrasound neuromodulation research.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are widely used for weight management and type 2 diabetes, but reports of reduced skin laxity and volume have raised aesthetic concerns. This study evaluates the first integrated skincare protocol designed for GLP-1 RA users. This 12-week, double-blind, randomized, split-face/split-neck study included 25 GLP-1 RA users (mean age 53.36 years) with mild-to-moderate skin aging, including male and female participants with Fitzpatrick skin types II to VI. All participants applied a topical regimen featuring Proxylane and wild fruit flavonoids (Flavo-Proxylane) to one side of the face/neck and a placebo to the other. After 4 weeks of topical monotherapy, participants received a single focused ultrasound treatment, followed by an additional 8 weeks of topical therapy. Outcomes included blinded image evaluation, 13 clinical grading parameters (via modified Griffiths scale), Global Aesthetic Improvement Scale scores, tolerability, and patient-reported satisfaction. All participants completed the study and lost an average of 3.7 lb. After 4 weeks of Flavo-Proxylane monotherapy, significant improvements were observed for facial skin laxity (- 16%; P < 0.001) and marionette lines (- 5%; P < 0.05), while no significant changes were observed with placebo. By week 12, the combined regimen achieved amplified improvements versus baseline, week 4, and placebo (all P < 0.001), with total reductions of 44% in skin laxity and 34% in marionette lines. Significant improvements were observed across all 13 clinical parameters. Overall improvement rating favored Flavo-Proxylane, with 94% reporting moderate-to-significant improvement versus 30% for placebo. Flavo-Proxylane treatment was well tolerated, with 84% reporting improved skin appearance and only three mild, self-resolving adverse events. This study demonstrates that an integrated regimen with Flavo-Proxylane products and ultrasound may improve aesthetic outcomes in a diverse range of participants undergoing GLP-1 RA treatment. Skin laxity, driven by collagen/elastin degradation and aging, is targeted by micro-focused ultrasound (MFU) through depth-specific thermal coagulation to induce collagen remodeling, yet parameter-dependent thermal kinetics and safety thresholds remain underexplored, limiting protocol optimization. To validate the dose-effect relationship of MFU using in vitro porcine skin tissues and evaluate its safety and efficacy for human facial skin tightening. Porcine skin tissues containing intact skin, fat, and muscle layers were treated with 8D-DL 3.0, 8D-DL 4.5, Vmax-DL 3.0, and Vmax-DL 4.5 handpieces. Subcutaneous temperatures at depths of 2.0 mm, 3.0 mm, 4.5 mm, and 6.0 mm were recorded under varying parameters (energy levels and exposure durations). Twenty patients undergoing single-session MFU facial treatment between June and August 2024 were enrolled. Skin tightening outcomes were assessed at 30- and 90-days post-treatment. For 8D-DL 3.0 and Vmax-DL 3.0 handpieces, peak temperatures occurred at 3.0 mm depth across all energy levels and exposure durations. For 8D-DL 4.5 and Vmax-DL 4.5 handpieces, peak temperatures localized at 4.5 mm. Focal depth temperatures increased significantly with higher energy levels and prolonged exposure. At 30- and 90-days post-treatment, upward displacement and volume reduction in bilateral cheek and jawline regions were observed. Mild procedural pain was reported, with no adverse events. MFU-induced thermal peaks align with preset focal depths, demonstrating parameter-dependent thermal accumulation. The procedure safely achieves clinically significant facial skin tightening. Transcranial focused ultrasound (tFUS) is an emerging noninvasive neuromodulation modality with the ability to target deep brain structures with high spatial precision. Despite its promise, rigorous evaluation of its efficacy is limited by the absence of reliable, fully double-blind sham methodologies. To develop and validate a pair of visually and mechanically indistinguishable acoustic coupling pads that enable true double-blind tFUS neuromodulation studies by providing either efficient ultrasound transmission or robust ultrasound blocking without altering participant or operator experience. Two coupling pads were engineered: a transmitting pad designed to allow <5% pressure amplitude loss relative to free-water propagation, and a non-transmitting pad designed to attenuate ultrasound by ≥40 dB. Both pads used a Dragon Skin 10 NV silicone base and were identical in size, appearance, flexibility, and handling. The non-transmitting pad incorporated an encapsulated air-based blocking layer using an open-cell polyethylene foam insert. Acoustic performance was evaluated in a water tank using a 650 kHz BrainSonix transducer and a calibrated needle hydrophone. Sound speed of the silicone material was measured using pulse-echo techniques. Twenty-three matched transmitting and non-transmitting pad pairs were fabricated and tested. Transmitting pads demonstrated a mean attenuation of -0.41 ± 0.53 dB, satisfying the design criterion of minimal acoustic loss. Non-transmitting pads demonstrated a mean attenuation of -48.61 ± 4.33 dB, exceeding the required -40 dB threshold for effective sham conditions. The Dragon Skin 10 NV substrate exhibited a sound speed of 964.72 m/s and produced <2 mm axial focal shift for standard pad thicknesses, with no measurable change in focal width. Both pad types were visually and tactually indistinguishable, could not be differentiated by experienced operators or participants, and maintained mechanical integrity after repeated cleaning. These acoustically engineered coupling pads provide a practical and validated solution for achieving true single- and double-blind conditions in tFUS neuromodulation studies. By preserving identical sensory and procedural experiences while enabling precise control over ultrasound transmission, this approach addresses a critical methodological gap in human ultrasound neuromodulation research.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are widely used for weight management and type 2 diabetes, but reports of reduced skin laxity and volume have raised aesthetic concerns. This study evaluates the first integrated skincare protocol designed for GLP-1 RA users. This 12-week, double-blind, randomized, split-face/split-neck study included 25 GLP-1 RA users (mean age 53.36 years) with mild-to-moderate skin aging, including male and female participants with Fitzpatrick skin types II to VI. All participants applied a topical regimen featuring Proxylane and wild fruit flavonoids (Flavo-Proxylane) to one side of the face/neck and a placebo to the other. After 4 weeks of topical monotherapy, participants received a single focused ultrasound treatment, followed by an additional 8 weeks of topical therapy. Outcomes included blinded image evaluation, 13 clinical grading parameters (via modified Griffiths scale), Global Aesthetic Improvement Scale scores, tolerability, and patient-reported satisfaction. All participants completed the study and lost an average of 3.7 lb. After 4 weeks of Flavo-Proxylane monotherapy, significant improvements were observed for facial skin laxity (- 16%; P < 0.001) and marionette lines (- 5%; P < 0.05), while no significant changes were observed with placebo. By week 12, the combined regimen achieved amplified improvements versus baseline, week 4, and placebo (all P < 0.001), with total reductions of 44% in skin laxity and 34% in marionette lines. Significant improvements were observed across all 13 clinical parameters. Overall improvement rating favored Flavo-Proxylane, with 94% reporting moderate-to-significant improvement versus 30% for placebo. Flavo-Proxylane treatment was well tolerated, with 84% reporting improved skin appearance and only three mild, self-resolving adverse events. This study demonstrates that an integrated regimen with Flavo-Proxylane products and ultrasound may improve aesthetic outcomes in a diverse range of participants undergoing GLP-1 RA treatment. Skin laxity, driven by collagen/elastin degradation and aging, is targeted by micro-focused ultrasound (MFU) through depth-specific thermal coagulation to induce collagen remodeling, yet parameter-dependent thermal kinetics and safety thresholds remain underexplored, limiting protocol optimization. To validate the dose-effect relationship of MFU using in vitro porcine skin tissues and evaluate its safety and efficacy for human facial skin tightening. Porcine skin tissues containing intact skin, fat, and muscle layers were treated with 8D-DL 3.0, 8D-DL 4.5, Vmax-DL 3.0, and Vmax-DL 4.5 handpieces. Subcutaneous temperatures at depths of 2.0 mm, 3.0 mm, 4.5 mm, and 6.0 mm were recorded under varying parameters (energy levels and exposure durations). Twenty patients undergoing single-session MFU facial treatment between June and August 2024 were enrolled. Skin tightening outcomes were assessed at 30- and 90-days post-treatment. For 8D-DL 3.0 and Vmax-DL 3.0 handpieces, peak temperatures occurred at 3.0 mm depth across all energy levels and exposure durations. For 8D-DL 4.5 and Vmax-DL 4.5 handpieces, peak temperatures localized at 4.5 mm. Focal depth temperatures increased significantly with higher energy levels and prolonged exposure. At 30- and 90-days post-treatment, upward displacement and volume reduction in bilateral cheek and jawline regions were observed. Mild procedural pain was reported, with no adverse events. MFU-induced thermal peaks align with preset focal depths, demonstrating parameter-dependent thermal accumulation. The procedure safely achieves clinically significant facial skin tightening. Transcranial focused ultrasound (tFUS) is an emerging noninvasive neuromodulation modality with the ability to target deep brain structures with high spatial precision. Despite its promise, rigorous evaluation of its efficacy is limited by the absence of reliable, fully double-blind sham methodologies. To develop and validate a pair of visually and mechanically indistinguishable acoustic coupling pads that enable true double-blind tFUS neuromodulation studies by providing either efficient ultrasound transmission or robust ultrasound blocking without altering participant or operator experience. Two coupling pads were engineered: a transmitting pad designed to allow <5% pressure amplitude loss relative to free-water propagation, and a non-transmitting pad designed to attenuate ultrasound by ≥40 dB. Both pads used a Dragon Skin 10 NV silicone base and were identical in size, appearance, flexibility, and handling. The non-transmitting pad incorporated an encapsulated air-based blocking layer using an open-cell polyethylene foam insert. Acoustic performance was evaluated in a water tank using a 650 kHz BrainSonix transducer and a calibrated needle hydrophone. Sound speed of the silicone material was measured using pulse-echo techniques. Twenty-three matched transmitting and non-transmitting pad pairs were fabricated and tested. Transmitting pads demonstrated a mean attenuation of -0.41 ± 0.53 dB, satisfying the design criterion of minimal acoustic loss. Non-transmitting pads demonstrated a mean attenuation of -48.61 ± 4.33 dB, exceeding the required -40 dB threshold for effective sham conditions. The Dragon Skin 10 NV substrate exhibited a sound speed of 964.72 m/s and produced <2 mm axial focal shift for standard pad thicknesses, with no measurable change in focal width. Both pad types were visually and tactually indistinguishable, could not be differentiated by experienced operators or participants, and maintained mechanical integrity after repeated cleaning. These acoustically engineered coupling pads provide a practical and validated solution for achieving true single- and double-blind conditions in tFUS neuromodulation studies. By preserving identical sensory and procedural experiences while enabling precise control over ultrasound transmission, this approach addresses a critical methodological gap in human ultrasound neuromodulation research.

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Botulinum toxin (BT) is used therapeutically since the late 1980s. For many years, BT drugs were provided by a small group of manufacturers from Europe and the United States. As BT's use for aesthetic purposes surged, numerous new manufacturers entered the field, particularly from Korea. We want to give an overview about the rapidly expanding and diversifying BT landscape in Korea. Altogether, there are 15 Korean manufacturers of 19 BT drugs registered in Korea, mainly for aesthetic indications. There are 2 Class 1 drugs from 2 Korean manufacturers registered in Korea for export, domestic use and registered in the USA and Europe. These are PrabotulinumtoxinA (Daewoong/Evolus) and LetibotulinumtoxinA (Hugel/Croma Pharma). There are 12 Class 2 drugs from 10 Korean manufacturers registered in Korea for export and domestic use, including Neuronox®, the first Korean BT drug registered in 2006, NivobotulinumtoxinA/Innotox®, the world-wide first liquid BT type A preparation and Coretox®, the world-wide second BT drug without complexing proteins. Innotox® and Toxsta® are currently performing clinical studies in the USA. Additionally, there are 5 Class 3 BT drugs from 5 Korean manufacturers registered in Korea for export use only. 5 Korean manufacturers have 5 drug projects in Korea in advanced development phases. With this, Korea is now the country with the worldwide largest number of BT manufacturers and BT drugs.

To compare the effectiveness of pixel CO2 laser and vaginal promestriene in treating genitourinary syndrome of menopause (GSM). A quasi-randomized controlled trial was conducted with 48 patients. CO2 Laser Group (24 patients) received 3 sessions of vaginal pixel CO2 laser, and promestriene group (24 patients) used vaginal promestriene daily for 14 days, then twice weekly for 3 months and 3 weeks. Patients were evaluated before and after treatment using a visual analog scale (VAS), FSFI-6, ICIQ-SF, Vaginal Health Index (VHI), and vaginal wall biopsy. Of the 48 patients, 22 in CO2 Laser Group and 21 in promestriene group completed the study. Both groups showed significant symptom reduction by VAS, with improvements in desire, lubrication, and total FSFI-6 scores. CO2 Laser Group had greater improvements in lubrication, orgasm, and satisfaction (p<0.001). Urinary incontinence improved in both groups (p<0.01). VHI scores increased significantly in both groups (p<0.001). Biopsies revealed improvements in collagen, glycogen, vascularity, epithelial thickness, and reduced neutrophil count (p<0.01). CO2 laser appears to be a viable non-hormonal alternative for treating GSM, particularly for women unable or unwilling to use hormonal therapies. Optical coherent tomography (OCT) is an emerging non-invasive imaging technology with significant potential in fields of medicine where invasive biopsy is limited or impractical. In ophthalmology, where retinal biopsy is not possible, OCT has become a standard of care for monitoring physiologic and pathologic changes. Similarly, OCT holds promise for improving women's healthcare, particularly in areas where biopsies are not routinely performed due to anatomical, ethical, or patient comfort considerations. Genitourinary syndrome of menopause (GSM) is one such condition where OCT may provide significant clinical value. However, ethical and practical limitations often restrict the ability to perform repeated or even sporadic vaginal wall biopsies. As a result, the efficacy of new treatment modalities largely assessed through subjective patient-reported outcomes, leading to inconsistent and controversial data that hinder progress in the field. This review outlines a collaborative effort by scientists and clinicians at the University of California, Irvine, to develop a novel, non-invasive "optical biopsy" tool for external genital assessment. A dedicated system integrated within a vaginal probe was developed to combine energy-based treatment with real-time OCT imaging. The new system successfully detected differences in vaginal epithelial thickness (VET) and blood vessel density (BVD) across women of different age groups, and between different segments of the vaginal wall. The system was used to measure VET and BVD changes before and after treatment with Fractional-Pixel CO2 laser. Beyond GSM, this technology is now being applied to other vulvovaginal conditions, including vulvar lichen sclerosus (VLS). The ability to perform non-invasive real-time monitoring of tissue structure and function is a critical step forward in women's health, offering new opportunities for diagnosis, treatment, monitoring, and ultimately improving clinical outcomes. Background: Our study aims to assess Pixel CO2 laser efficacy for female stress urinary incontinence (SUI). Methods: In the study, 25 women with SUI were included and scheduled for vaginal Pixel CO2 Laser (FemiLift™, Alma Lasers, Israel) treatment. All subjects had a baseline and 6-month post-treatment assessment that included three-dimensional perineal ultrasound and validated questionnaires. Results: Data showed that monthly three-session vaginal Pixel CO2 Laser treatment significantly improved SUI symptoms, as evidenced by validated questionnaires, including UDI-6, IIQ-7, ICIQ, and vaginal laxity questionnaire (p < 0.05). The Pixel CO2 Laser efficacy in vaginal treatment was 20/25 (80%), and the perineal sonography showed that laser treatment significantly decreased bladder neck mobility and middle urethral area (during resting and straining). Permanent adverse events were not found. Conclusions: The results of our study suggested that for the treatment of mild to moderate SUI symptoms, Pixel CO2 Laser is effective and safe; however, more studies and a longer follow-up should be conducted to confirm its efficacy and durability. The aim of this study was to assess the safety and efficacy of a minimally invasive pixel-CO2 laser procedure for the treatment of stress urinary incontinence (SUI). This was a prospective, open-label study with a cohort of 59 women. Patients were treated intravaginally with a fractional/pixel CO2 laser every 4-6 weeks for a total of three treatments and assessed at 3, 6, and 12 months. Evaluation tools included a Sandvik severity score based on a validated questionnaire, 1-h pad test, vaginal health index score (VHIS), validated female sexual function index (FSFI), patient's impression of disease severity (PGI-S), global impression of improvement (PGI-I), and the short-term pelvic floor impact questionnaire (PFIQ-7) to assess improvements in quality of life. Reduction in SUI severity was noticed throughout the duration of the study, as compared to the baseline in which 2% of the patients were defined as "slight," 73% "moderate," and 25% "severe." Gradual improvement of symptoms resulted in redistribution of severity score and the best outcome observed between 3 and 6 months. Sanitary pad weight declined from an average of 35.45 g per day at baseline to 12.47 g at the 3rd treatment, and increased to 23.06 g at 12 months. Vaginal acidity changes showed a similar pattern. No serious adverse events were reported. Pixel-CO2 laser is safe and effective for treating SUI. Additional maintenance treatments should be considered during the 6-12-month post-treatment period in order to maintain the beneficial effects. Pixel-CO2 laser is a safe and effective treatment for SUI. Maintenance treatments should be considered at 6-12 months. Energy-based treatments have been found to be a promising treatment modality for improving stress urinary incontinence (SUI) symptoms. This prospective two-center study was designed to evaluate the efficacy of fractional-pixel CO2 laser for the treatment of SUI. Eighty-five women with SUI symptoms as per the cough stress test and validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), were treated intravaginally with Pixel-CO2 laser. Two treatment sessions were performed with a 1-month interval. Safety and treatment tolerance were assessed by the visual analog scale (VAS) immediately and at 1 week after each laser treatment. Associations of age and body mass index (BMI) with the ICIQ-UI-SF score were statistically assessed by the Jonckheere-Terpstra test. The ICIQ-UI-SF score was 12.0 at baseline, 7.0, after the first treatment, and 3.5 after the second treatment (P = 0.001). For women with BMI (25.0-29.9), the ICIQ-UI-SF score was 9.0 at the baseline, 6.0 after 1 month, and 5.0 at the 6 months follow-up visit (P = 0.04). For women with BMI ≥ 30.0, the ICIQ-UI-SF score was reduced from 14.0 to 8.0 1 month after the baseline and 5.0 at the 6-month follow-up visit (P = 0.001). SUI severity evaluation at baseline showed that 27.1% of women had mild, 24.7% had moderate, 45.9% had severe, and 2.4% had very severe SUI symptoms. SUI severity scores were significantly reduced, with 45.8% of women with no SUI symptoms, 18.8% with mild, 20.8% with moderate, and 14.6% with severe SUI symptoms at the 6-month follow-up. The patient's evaluation of VAS after the first treatment was 1.0-1.5 (0-10) and 0.0 1 week after the second treatment. Fractional-pixel CO2 laser is safe and effective for treating SUI. No adverse event or significant pain was reported during or after the

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

The increasing demand for removable dentures among the geriatric population underscores the need for safe and effective denture cleansers and adhesives. Concerns over the toxicity, cost, and limited biocompatibility of conventional chemical-based products have led to increasing interest in herbal alternatives. This systematic review assessed the efficacy and safety of herbal extracts in denture care. A comprehensive search of PubMed, ScienceDirect, Wiley Online Library, and the Cochrane Library was conducted using the terms "herbal denture cleansers," "herbal denture adhesives," and "denture care." In vivo studies published in English since 2010 were included, and seven studies met the inclusion criteria. Herbal agents such as Neem, Triphala, Aloe vera, turmeric, and olive oil demonstrated significant antifungal and antimicrobial activity, comparable to commercial formulations, along with improved denture retention and mucosal health. Overall, herbal extracts hold promise as effective, safe, and biocompatible alternatives for denture maintenance and patient comfort. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by malignancy derived from hematopoietic stem cells. Compared with polycythemia vera (PV) and essential thrombocythemia (ET), PMF shows a worse clinical prognosis. Therefore, it is essential to explore biological markers for early identification and intervention to delay the process of the disease. Megakaryocytes (MK) play a central role in the pathogenesis and disease progression of PMF. The thrombophilia, the aggravation of myelofibrosis and the transformation to acute myeloid leukemia (AML) in patients with PMF are closely related to the morphological characteristics of MK.Changes in MK morphology are not only regulated by inflammatory mediators, but also influenced by specific genetic factors. This article will review the mechanism of MK morphological changes in PMF and the latest research progress on the prognosis of PMF with MK morphology, so as to provide reference for early clinical diagnosis and treatment. 巨核细胞形态在原发性骨髓纤维化预后中的研究进展. 原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤（MPN），其特征是源自造血干细胞的恶性肿瘤。相较于真性红细胞增多症和原发性血小板增多症，PMF展现出更为不良的临床预后，因此，探寻能够早期识别并干预的生物学标志，对于延缓疾病进程至关重要。巨核细胞（MK）在PMF的发病机制和疾病进展中扮演着核心角色。PMF患者的血栓形成倾向、骨髓纤维化程度的加剧以及向急性髓系白血病的转化，均与MK的形态学特征密切相关。MK形态的变化不仅受到炎症介质的调控，还受到特定遗传因素的影响。本文将对PMF中MK形态变化的机制和MK形态对PMF预后的最新研究做一综述，为临床诊疗提供了早期判断的参考依据. This study aimed to develop, characterize, and clinically evaluate a novel 6% nitroglycerin (NTG) Aloe vera gel formulation as a transdermal alternative to conventional sublingual NTG therapy in patients with stable angina pectoris. A randomized, parallel-group, double-blind clinical trial was conducted involving 150 patients with stable angina, allocated to receive either 6% NTG-Aloe vera gel or standard sublingual NTG tablets (0.6mg). The gel was assessed for physicochemical parameters, FTIR compatibility, stability under ICH guidelines, and in vitro drug release kinetics. Dermatological safety was evaluated via skin irritation testing. Clinical efficacy was determined by Numeric Pain Rating Scale (NPRS), chest tightness scores, Seattle Angina Questionnaire (SAQ), and vital parameters, including blood pressure and oxygen saturation. The NTG Aloe vera gel demonstrated desirable physicochemical properties, sustained zero-order drug release, and excellent stability with no significant degradation. Clinical data revealed that the gel provided gradual, sustained pain and chest tightness relief, superior SAQ scores (p<0.001), and improved tolerability compared to sublingual NTG. Importantly, the gel induced a controlled hypotensive response without abrupt cardiovascular changes, indicating enhanced safety. No dermatological adverse effects were reported. This pilot study showed 6% NTG-Aloe vera gel offers a stable, effective, and patient-friendly transdermal delivery system for angina management, meriting further large-scale and long-term evaluations. Clinical Trial Registry-India (CTRI/2024/11/076947). Globally, the incidence and prevalence of skin cancer have increased. Skin cancers involve an abnormal growth of cells. Skin cancers are classified into melanoma and nonmelanoma skin cancer (NMSC), and NMSC is further classified as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In the present narrative review, we searched databases, such as PubMed, Scopus, and Google Scholar, to retrieve the relevant articles. The ideal selection of therapeutic options depends on the anatomical location, genetic composition, different tumor stages, the individual's age, and general health conditions. Various chemotherapeutic options are available for effective treatment, but there are various side effects of the drugs. Natural products (NPs) may be used as supplements. NPs can potentiate apoptosis, decrease cell growth, and prevent metastasis. They are also safe and effective. The present review summarizes the use of natural products, such as Aloe vera, eggplant, frankincense, milk thistle, turmeric, black raspberry, mistletoe, burdock root, Dong Quai, black salve, astragalus, Solanum sodomaeum, Calendula officinalis, Melaleuca alternifolia, Hypericum perforatum, Withania somnifera, Polypodium leucotomos, Rosmarinus officinalis, Alpinia galangal, hypericin, tea, coffee, genistein, grape seed, and silymarin. Larger clinical trials are needed to explore the safety profile of various natural products that have proven effective against skin cancer. Periodontitis is a highly prevalent chronic inflammatory disease initiated by dysbiotic biofilms and sustained by an exaggerated host immune response, for which scaling and root planing (SRP) remains the cornerstone of therapy. However, mechanical debridement alone may be insufficient to fully resolve inflammation in complex cases and in susceptible patients. In this context, natural products and host modulatory strategies have emerged as potential adjunctive therapies owing to their antimicrobial, anti-inflammatory, antioxidant,

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Microsatellites stability (MSS) colon cancer patients exhibit a significant suppressive immune status, and the functional status of tumor NLRP3 immunosomes plays an important role in regulating the tumor immune microenvironment, but whether they are involved in the regulation of immunosuppression in MSS patients is unclear. Therefore, further exploration of the relevant molecular mechanisms is urgently needed. The Cancer Genome Atlas-Colorectal Cancer (TCGA-COAD) Masked Somatic Mutation data, clinicopathological data were obtained, analyzed, and visualized using the 'maftools' in R package. Tissue microarray (TMA) used for this study includes 100 unselected, non-consecutive, primary, and sporadic CRCs treated between April 2006 and October 2010 in Tianjin Medical University General Hospital and 60 adjacent noncancerous tissues. Demographic and clinicopathological variables were collected, and the clinical value and prognostic impact of NLRP3 expression were analyzed. Tissue immunofluorescence (IF) was applied to investigate the colocalization expression of NLRP3 and ASC in tumor cells. The Vectra 3.0 Automated Quantitative Pathology Imaging System was used to obtain spectral information the NLRP3-ASC colocalization was analyzed by the Fiji Plugin "Coloc2". Cytotoxic T lymphocytes and M2 macrophages in tumor tissue were evaluated by immunohistochemistry. In patients with MSS-CRC, aberrant activation of NLRP3 immunosome was significantly associated with lymph node metastasis of tumors. It is also closely related to the polarization of M2 macrophages in the tumor microenvironment, and further affects the infiltration of CD8+T lymphocytes, thereby creating a suppressive immune microenvironment. Localized scleroderma (LSc) is an autoimmune condition characterized by localized cutaneous sclerosis, sometimes extending into deeper tissues. Phototherapy, including excimer laser therapy (ELT), is considered an effective and minimally invasive treatment option for patients without extracutaneous involvement. However, little is known about the histopathological and molecular alterations that occur during treatment. Here, we report a case of circumscribed morphea successfully treated with ELT, accompanied by detailed longitudinal histological analysis. A 78-year-old woman presented with gradually progressive indurated plaques on both sides of the abdomen. Histopathological examination of the lesional skin revealed dense collagen deposition and perivascular infiltration of lymphocytes, monocytes, and mast cells, confirming the diagnosis of circumscribed morphea. Topical glucocorticoid therapy yielded insufficient improvement, prompting the addition of 308-nm ELT. The patient underwent 12 ELT sessions, administered every two to four weeks with incremental dosing from 100 mJ/cm2 to 240 mJ/cm2, reaching a cumulative dose of 2100 mJ/cm2. This regimen resulted in marked clinical improvement within one year. Post-treatment biopsies demonstrated near-complete resolution of dermal sclerosis, with substantial reductions in inflammatory cell infiltration. Toluidine blue staining and immunohistochemistry further revealed dynamic cellular changes: mast cells and CD3+ T cells were significantly decreased; CD34 expression, absent in lesional dermal mesenchymal cells before treatment, was restored; and α-smooth muscle actin-positive myofibroblasts, abundant at baseline, were markedly reduced following ELT. These findings indicate that ELT not only ameliorates clinical sclerosis but also reverses immune and mesenchymal cell alterations associated with fibrosis. This case highlights the therapeutic potential of ELT in circumscribed morphea and suggests a plausible mechanism by which ELT modulates immune-mesenchymal interactions to attenuate fibrosis in LSc. Although most rhinovirus infections are mild and subside quickly, vulnerable populations may experience severe illness. Identifying populations at risk for severe or complicated rhinovirus illness can strengthen the ongoing search for preventative and therapeutic treatments. This systematic review and meta-analysis aimed to summarize the populations at risk for the development of severe or complicated rhinovirus illness. We searched CENTRAL, EMBASE, and MEDLINE in April 2024 for studies reporting risk factors for severe rhinovirus infection, defined as lower respiratory tract infection (LRTI), hospitalization, critical care unit (CCU) admission, mechanical ventilation, or death. We pooled odds ratios using random-effects meta-analysis, assessed risk of bias using the Newcastle-Ottawa Scale, and rated the certainty of evidence using the GRADE framework. From 29 observational studies (n = 13,185 participants), we analyzed 13 risk factor-outcome combinations. With high certainty, age < 1 year and premature birth are not associated with the risk of LRTI, and diabetes mellitus is not associated with mortality. With moderate certainty, any comorbidity and pulmonary comorbidity are probably associated with increased risk of LRTI, age > 18 years and malignancy are probably associated with increased risk of mortality, and malignancy is probably associated with an increased risk of CCU admission. Many risk factors lacked sufficient evidence for meta-analysis. Individuals with comorbidities are at greater risk of severe rhinovirus illness. Our findings can inform clinical risk stratification and guide the development and targeted use of emerging therapies. Further comprehensive research is required to elucidate additional risk factors and strengthen the evidence. Dental implant failure is influenced by anatomical, systemic, and procedural factors. This study assessed the predictive value of machine learning models: logistic regression, Random Forest, and gradient boosting, using an open-access dataset (Liu et al. 2018) containing demographic, surgical, prosthetic, and systemic variables. Random Forest performed best (accuracy 0.85, ROC-AUC 0.79, F1 = 0.92, recall 0.97), followed by gradient boosting, while logistic regression showed lower sensitivity. Feature importance analysis identified implant location, sinus augmentation, implant dimensions, and patient age as key predictors. Ensemble models and interpretable feature metrics demonstrate strong potential for improving clinical risk stratification in implant dentistry. This study presents a comprehensive phytochemical investigation of the stems of Syringa oblata Lindl., leading to the isolation and structural characterization of fourteen previously undescribed compounds, including ten sesquiterpenoids (oblatiosides H-M and syringanoids A-D) and four lignans (syringalignans A-D). Their structures and absolute configurations were rigorously established through extensive spectroscopic analyses (HR-ESI-MS and 1D/2D NMR) and comparative electronic circular dichroism (ECD) calculations. In bioactivity evaluations, most compounds demonstrated significant inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with syringalignan D (14), oblatioside K (4), and oblatioside I (2) exhibiting the strongest anti-inflammatory effects (IC50 = 12.5 ± 0.79, 15.2 ± 0.98, and 21.1 ± 0.86 µM, respectively), comparable to dexamethasone (IC50 = 35.4 ± 0.39 µM). Additionally, syringalignan B (12) and syringalignan D (14) displayed potent antioxidant activity in the DPPH assay (IC50 = 13.0 ± 0.48 and 22.6 ± 1.12 µM), outperforming several sesquiterpenoids and approaching the activity of ascorbic acid (IC50 = 23.5 ± 0.46 µM). Notably, compound 14 dose-dependently (5-20 µM) suppressed LPS-stimulated ROS generation and lowered IL-6, TNF-α, and IL-1β mRNA levels in RAW264.7 cells, while also markedly reducing phosphorylated P65, JNK, and Erk proteins, indicating potent anti-oxidant and anti-inflammatory activity. These fi

Microsatellites stability (MSS) colon cancer patients exhibit a significant suppressive immune status, and the functional status of tumor NLRP3 immunosomes plays an important role in regulating the tumor immune microenvironment, but whether they are involved in the regulation of immunosuppression in MSS patients is unclear. Therefore, further exploration of the relevant molecular mechanisms is urgently needed. The Cancer Genome Atlas-Colorectal Cancer (TCGA-COAD) Masked Somatic Mutation data, clinicopathological data were obtained, analyzed, and visualized using the 'maftools' in R package. Tissue microarray (TMA) used for this study includes 100 unselected, non-consecutive, primary, and sporadic CRCs treated between April 2006 and October 2010 in Tianjin Medical University General Hospital and 60 adjacent noncancerous tissues. Demographic and clinicopathological variables were collected, and the clinical value and prognostic impact of NLRP3 expression were analyzed. Tissue immunofluorescence (IF) was applied to investigate the colocalization expression of NLRP3 and ASC in tumor cells. The Vectra 3.0 Automated Quantitative Pathology Imaging System was used to obtain spectral information the NLRP3-ASC colocalization was analyzed by the Fiji Plugin "Coloc2". Cytotoxic T lymphocytes and M2 macrophages in tumor tissue were evaluated by immunohistochemistry. In patients with MSS-CRC, aberrant activation of NLRP3 immunosome was significantly associated with lymph node metastasis of tumors. It is also closely related to the polarization of M2 macrophages in the tumor microenvironment, and further affects the infiltration of CD8+T lymphocytes, thereby creating a suppressive immune microenvironment. Localized scleroderma (LSc) is an autoimmune condition characterized by localized cutaneous sclerosis, sometimes extending into deeper tissues. Phototherapy, including excimer laser therapy (ELT), is considered an effective and minimally invasive treatment option for patients without extracutaneous involvement. However, little is known about the histopathological and molecular alterations that occur during treatment. Here, we report a case of circumscribed morphea successfully treated with ELT, accompanied by detailed longitudinal histological analysis. A 78-year-old woman presented with gradually progressive indurated plaques on both sides of the abdomen. Histopathological examination of the lesional skin revealed dense collagen deposition and perivascular infiltration of lymphocytes, monocytes, and mast cells, confirming the diagnosis of circumscribed morphea. Topical glucocorticoid therapy yielded insufficient improvement, prompting the addition of 308-nm ELT. The patient underwent 12 ELT sessions, administered every two to four weeks with incremental dosing from 100 mJ/cm2 to 240 mJ/cm2, reaching a cumulative dose of 2100 mJ/cm2. This regimen resulted in marked clinical improvement within one year. Post-treatment biopsies demonstrated near-complete resolution of dermal sclerosis, with substantial reductions in inflammatory cell infiltration. Toluidine blue staining and immunohistochemistry further revealed dynamic cellular changes: mast cells and CD3+ T cells were significantly decreased; CD34 expression, absent in lesional dermal mesenchymal cells before treatment, was restored; and α-smooth muscle actin-positive myofibroblasts, abundant at baseline, were markedly reduced following ELT. These findings indicate that ELT not only ameliorates clinical sclerosis but also reverses immune and mesenchymal cell alterations associated with fibrosis. This case highlights the therapeutic potential of ELT in circumscribed morphea and suggests a plausible mechanism by which ELT modulates immune-mesenchymal interactions to attenuate fibrosis in LSc. Although most rhinovirus infections are mild and subside quickly, vulnerable populations may experience severe illness. Identifying populations at risk for severe or complicated rhinovirus illness can strengthen the ongoing search for preventative and therapeutic treatments. This systematic review and meta-analysis aimed to summarize the populations at risk for the development of severe or complicated rhinovirus illness. We searched CENTRAL, EMBASE, and MEDLINE in April 2024 for studies reporting risk factors for severe rhinovirus infection, defined as lower respiratory tract infection (LRTI), hospitalization, critical care unit (CCU) admission, mechanical ventilation, or death. We pooled odds ratios using random-effects meta-analysis, assessed risk of bias using the Newcastle-Ottawa Scale, and rated the certainty of evidence using the GRADE framework. From 29 observational studies (n = 13,185 participants), we analyzed 13 risk factor-outcome combinations. With high certainty, age < 1 year and premature birth are not associated with the risk of LRTI, and diabetes mellitus is not associated with mortality. With moderate certainty, any comorbidity and pulmonary comorbidity are probably associated with increased risk of LRTI, age > 18 years and malignancy are probably associated with increased risk of mortality, and malignancy is probably associated with an increased risk of CCU admission. Many risk factors lacked sufficient evidence for meta-analysis. Individuals with comorbidities are at greater risk of severe rhinovirus illness. Our findings can inform clinical risk stratification and guide the development and targeted use of emerging therapies. Further comprehensive research is required to elucidate additional risk factors and strengthen the evidence. Dental implant failure is influenced by anatomical, systemic, and procedural factors. This study assessed the predictive value of machine learning models: logistic regression, Random Forest, and gradient boosting, using an open-access dataset (Liu et al. 2018) containing demographic, surgical, prosthetic, and systemic variables. Random Forest performed best (accuracy 0.85, ROC-AUC 0.79, F1 = 0.92, recall 0.97), followed by gradient boosting, while logistic regression showed lower sensitivity. Feature importance analysis identified implant location, sinus augmentation, implant dimensions, and patient age as key predictors. Ensemble models and interpretable feature metrics demonstrate strong potential for improving clinical risk stratification in implant dentistry. This study presents a comprehensive phytochemical investigation of the stems of Syringa oblata Lindl., leading to the isolation and structural characterization of fourteen previously undescribed compounds, including ten sesquiterpenoids (oblatiosides H-M and syringanoids A-D) and four lignans (syringalignans A-D). Their structures and absolute configurations were rigorously established through extensive spectroscopic analyses (HR-ESI-MS and 1D/2D NMR) and comparative electronic circular dichroism (ECD) calculations. In bioactivity evaluations, most compounds demonstrated significant inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with syringalignan D (14), oblatioside K (4), and oblatioside I (2) exhibiting the strongest anti-inflammatory effects (IC50 = 12.5 ± 0.79, 15.2 ± 0.98, and 21.1 ± 0.86 µM, respectively), comparable to dexamethasone (IC50 = 35.4 ± 0.39 µM). Additionally, syringalignan B (12) and syringalignan D (14) displayed potent antioxidant activity in the DPPH assay (IC50 = 13.0 ± 0.48 and 22.6 ± 1.12 µM), outperforming several sesquiterpenoids and approaching the activity of ascorbic acid (IC50 = 23.5 ± 0.46 µM). Notably, compound 14 dose-dependently (5-20 µM) suppressed LPS-stimulated ROS generation and lowered IL-6, TNF-α, and IL-1β mRNA levels in RAW264.7 cells, while also markedly reducing phosphorylated P65, JNK, and Erk proteins, indicating potent anti-oxidant and anti-inflammatory activity. These fi

Microsatellites stability (MSS) colon cancer patients exhibit a significant suppressive immune status, and the functional status of tumor NLRP3 immunosomes plays an important role in regulating the tumor immune microenvironment, but whether they are involved in the regulation of immunosuppression in MSS patients is unclear. Therefore, further exploration of the relevant molecular mechanisms is urgently needed. The Cancer Genome Atlas-Colorectal Cancer (TCGA-COAD) Masked Somatic Mutation data, clinicopathological data were obtained, analyzed, and visualized using the 'maftools' in R package. Tissue microarray (TMA) used for this study includes 100 unselected, non-consecutive, primary, and sporadic CRCs treated between April 2006 and October 2010 in Tianjin Medical University General Hospital and 60 adjacent noncancerous tissues. Demographic and clinicopathological variables were collected, and the clinical value and prognostic impact of NLRP3 expression were analyzed. Tissue immunofluorescence (IF) was applied to investigate the colocalization expression of NLRP3 and ASC in tumor cells. The Vectra 3.0 Automated Quantitative Pathology Imaging System was used to obtain spectral information the NLRP3-ASC colocalization was analyzed by the Fiji Plugin "Coloc2". Cytotoxic T lymphocytes and M2 macrophages in tumor tissue were evaluated by immunohistochemistry. In patients with MSS-CRC, aberrant activation of NLRP3 immunosome was significantly associated with lymph node metastasis of tumors. It is also closely related to the polarization of M2 macrophages in the tumor microenvironment, and further affects the infiltration of CD8+T lymphocytes, thereby creating a suppressive immune microenvironment. Localized scleroderma (LSc) is an autoimmune condition characterized by localized cutaneous sclerosis, sometimes extending into deeper tissues. Phototherapy, including excimer laser therapy (ELT), is considered an effective and minimally invasive treatment option for patients without extracutaneous involvement. However, little is known about the histopathological and molecular alterations that occur during treatment. Here, we report a case of circumscribed morphea successfully treated with ELT, accompanied by detailed longitudinal histological analysis. A 78-year-old woman presented with gradually progressive indurated plaques on both sides of the abdomen. Histopathological examination of the lesional skin revealed dense collagen deposition and perivascular infiltration of lymphocytes, monocytes, and mast cells, confirming the diagnosis of circumscribed morphea. Topical glucocorticoid therapy yielded insufficient improvement, prompting the addition of 308-nm ELT. The patient underwent 12 ELT sessions, administered every two to four weeks with incremental dosing from 100 mJ/cm2 to 240 mJ/cm2, reaching a cumulative dose of 2100 mJ/cm2. This regimen resulted in marked clinical improvement within one year. Post-treatment biopsies demonstrated near-complete resolution of dermal sclerosis, with substantial reductions in inflammatory cell infiltration. Toluidine blue staining and immunohistochemistry further revealed dynamic cellular changes: mast cells and CD3+ T cells were significantly decreased; CD34 expression, absent in lesional dermal mesenchymal cells before treatment, was restored; and α-smooth muscle actin-positive myofibroblasts, abundant at baseline, were markedly reduced following ELT. These findings indicate that ELT not only ameliorates clinical sclerosis but also reverses immune and mesenchymal cell alterations associated with fibrosis. This case highlights the therapeutic potential of ELT in circumscribed morphea and suggests a plausible mechanism by which ELT modulates immune-mesenchymal interactions to attenuate fibrosis in LSc. Although most rhinovirus infections are mild and subside quickly, vulnerable populations may experience severe illness. Identifying populations at risk for severe or complicated rhinovirus illness can strengthen the ongoing search for preventative and therapeutic treatments. This systematic review and meta-analysis aimed to summarize the populations at risk for the development of severe or complicated rhinovirus illness. We searched CENTRAL, EMBASE, and MEDLINE in April 2024 for studies reporting risk factors for severe rhinovirus infection, defined as lower respiratory tract infection (LRTI), hospitalization, critical care unit (CCU) admission, mechanical ventilation, or death. We pooled odds ratios using random-effects meta-analysis, assessed risk of bias using the Newcastle-Ottawa Scale, and rated the certainty of evidence using the GRADE framework. From 29 observational studies (n = 13,185 participants), we analyzed 13 risk factor-outcome combinations. With high certainty, age < 1 year and premature birth are not associated with the risk of LRTI, and diabetes mellitus is not associated with mortality. With moderate certainty, any comorbidity and pulmonary comorbidity are probably associated with increased risk of LRTI, age > 18 years and malignancy are probably associated with increased risk of mortality, and malignancy is probably associated with an increased risk of CCU admission. Many risk factors lacked sufficient evidence for meta-analysis. Individuals with comorbidities are at greater risk of severe rhinovirus illness. Our findings can inform clinical risk stratification and guide the development and targeted use of emerging therapies. Further comprehensive research is required to elucidate additional risk factors and strengthen the evidence. Dental implant failure is influenced by anatomical, systemic, and procedural factors. This study assessed the predictive value of machine learning models: logistic regression, Random Forest, and gradient boosting, using an open-access dataset (Liu et al. 2018) containing demographic, surgical, prosthetic, and systemic variables. Random Forest performed best (accuracy 0.85, ROC-AUC 0.79, F1 = 0.92, recall 0.97), followed by gradient boosting, while logistic regression showed lower sensitivity. Feature importance analysis identified implant location, sinus augmentation, implant dimensions, and patient age as key predictors. Ensemble models and interpretable feature metrics demonstrate strong potential for improving clinical risk stratification in implant dentistry. This study presents a comprehensive phytochemical investigation of the stems of Syringa oblata Lindl., leading to the isolation and structural characterization of fourteen previously undescribed compounds, including ten sesquiterpenoids (oblatiosides H-M and syringanoids A-D) and four lignans (syringalignans A-D). Their structures and absolute configurations were rigorously established through extensive spectroscopic analyses (HR-ESI-MS and 1D/2D NMR) and comparative electronic circular dichroism (ECD) calculations. In bioactivity evaluations, most compounds demonstrated significant inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with syringalignan D (14), oblatioside K (4), and oblatioside I (2) exhibiting the strongest anti-inflammatory effects (IC50 = 12.5 ± 0.79, 15.2 ± 0.98, and 21.1 ± 0.86 µM, respectively), comparable to dexamethasone (IC50 = 35.4 ± 0.39 µM). Additionally, syringalignan B (12) and syringalignan D (14) displayed potent antioxidant activity in the DPPH assay (IC50 = 13.0 ± 0.48 and 22.6 ± 1.12 µM), outperforming several sesquiterpenoids and approaching the activity of ascorbic acid (IC50 = 23.5 ± 0.46 µM). Notably, compound 14 dose-dependently (5-20 µM) suppressed LPS-stimulated ROS generation and lowered IL-6, TNF-α, and IL-1β mRNA levels in RAW264.7 cells, while also markedly reducing phosphorylated P65, JNK, and Erk proteins, indicating potent anti-oxidant and anti-inflammatory activity. These fi

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

The infraorbital hollow and midcheek groove ("Indian bands") are anatomically complex transition zones where ligamentous, vascular, and fat compartments converge. Safe and predictable correction with hyaluronic acid (HA) fillers requires precise, layer-specific anatomical understanding. To synthesize anatomy-based injection strategies for the infraorbital-midcheek continuum, including diagnostic triage, technique selection, complication mitigation, and ethnic-specific considerations. We conducted a narrative review based on a structured search of MEDLINE, PubMed, and Ovid databases using predefined keywords related to "Dark Circle," "Midcheek Groove," "Indian Band," "Dermal Fillers," and "Facial Anatomy." Eligible anatomical dissections, imaging-based mappings, and clinical outcome studies were qualitatively synthesized; no original patient data were collected, and no PRISMA flow diagram or quantitative meta-analysis was performed. Cannula-assisted subcision to partially release fibrous retaining bands, followed by deep support (deep malar fat pad/suborbicularis oculi fat [SOOF]) and selective superficial blending, appears to improve midcheek groove correction in published series using Maili Volume and Precise. Management of overfill or surface irregularity relies on hyaluronidase and an understanding of product rheology (elastic modulus G', cohesivity, elasticity). However, the available evidence remains heterogeneous and predominantly case-series level, with limited standardized outcomes, patient-reported measures, and long-term follow-up. An anatomy-based, layer-specific approach can enhance predictability and safety for infraorbital-midcheek rejuvenation, but current recommendations are largely experience-driven. Future work should prioritize controlled clinical validation, complication registries, and population-specific optimization of technique with robust, quantitative and patient-centered outcomes. Forehead filler injections have become a popular nonsurgical approach to enhance facial aesthetics by correcting volume deficiencies and improving contours. This anatomy-based approach emphasizes the importance of understanding the complex structural components of the forehead, including fat compartments, muscles, and vascular pathways. Proper diagnosis of forehead depressions-categorized as central, bilateral, mixed, or total types-guides targeted treatment strategies using submuscular or subdermal injection planes. Submuscular injections provide structural support, minimizing risks associated with superficial placement, such as uneven distribution and vascular complications. Techniques tailored to specific anatomic features, particularly in East Asian patients who often present with narrower foreheads, ensure natural and balanced results. Fillers used in this paper are Hyaluronic Acid (Maili, Sinclair) and Polycaprolactone (Ellanse, Sinclair). Combining fillers with botulinum toxin injections can address both dynamic and static wrinkles, achieving comprehensive facial rejuvenation while maintaining natural expressions, which is especially true for Polycaprolactone biostimulator fillers. This integrated approach optimizes aesthetic outcomes and enhances patient satisfaction by delivering smooth, contoured, and youthful forehead appearances. Level of Evidence: Level V. The shape and size of ears significantly influence facial aesthetics. In many Asian cultures, lying ears are not perceived favorably in Asian culture, leading individuals to seek surgical interventions to correct this issue. Also, due to the Ebbinghaus effect, prominent ears create a illusion of a smaller face, which is highly desired in Asians. However, surgeries to create prominent ears are invasive, can involve complications and necessitate a period of recovery. To address this concern, the authors have developed a technique utilizing hyaluronic acid (HA) injections of MAILI range (Sinclair Pharma) to enhance the appearance of lying ears. HA injections were performed at the auriculocephalic sulcus and the helix to increase the cranioauricular angle (CA) and correct lying ears. Patients showed improvements in ear prominence. The cranioauricular angle (CAA) and ear projection (EP) increased immediately after the procedure. No serious complications were noted. The injection of hyaluronic acid (HA) into the ears successfully addressed the issue of lying ears and enhanced the overall facial profile. In addition, it provided a lifting effect that contributed to a more youthful and refined appearance. This minimally invasive procedure did not necessitate any recovery time, and the results were long-lasting and highly satisfactory. Level V. Nasolabial folds significantly impact facial appearance and are a common aesthetic concern. This article reviews anatomic considerations and filler injection techniques for treating these folds, with a focus on the Korean population. The dermal filler used in this study is Maili hyaluronic acid filler (Sinclair Pharma), derived from a novel proprietary manufacturing technology known as OxiFree™ technology (Kylane Laboratoires , Switzerland). The study analyzes various injection techniques, including needle-based and cannula-based approaches, with emphasis on safe and effective practices such as the Fern leaf and Duck walk techniques. A layered injection approach addressing both superficial and deep tissue planes is examined. Three distinct types of nasolabial folds are identified: those caused by volume deficiency, tissue laxity, and muscular attachments. Each type requires a tailored treatment approach. It is not uncommon to find a combination of 2 of the types together in one person. The study highlights the importance of understanding anatomic variations, particularly the course of the facial artery in the Korean population, for safe injection practices. A thorough understanding of nasolabial fold anatomy and appropriate treatment strategies is crucial for achieving optimal outcomes in aesthetic medicine. This is especially important for the nasolabial folds, which are highly mobile, and could easily cause misplaced dermal fillers to migrate. Future research on combination intervention techniques, including botulinum toxin, lipolytic agents, and thread-lifting, may further enhance overall treatment efficacy. Facial asymmetry is a common challenge in esthetic medicine, requiring a comprehensive understanding of three-dimensional rotation patterns- X, Y , and Z axes-that significantly influence treatment outcomes. Traditional correction methods often overlook these rotational dynamics. This manuscript presents a case study of a 38-year-old Asian male patient with facial asymmetry, treated with hyaluronic acid (HA) fillers using a novel approach incorporating facial rotation concepts. By identifying the patient's clockwise facial rotation pattern and applying targeted, asymmetric filler placement, a significant improvement in facial harmony was achieved. The rheological properties of the MaiLi Extreme (Sinclair) were particularly suited for structural correction. This approach highlights the importance of rotation-based assessment and personalised treatment planning in achieving optimal esthetic outcomes.

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy through the TLR9 signaling pathway for HSV-2 infection treatment. This study provides an effective research strategy to further explore the mechanism of this traditional Chinese medicine (TCM) for preventing and treating diseases. IL-6 is the primary mediator of inflammation. It can be secreted by immune cells, tumor cells, and stromal cells, which is highly expressed in tissues from tumors. Through its downstream signaling pathway, IL-6 regulates nearly every aspect of the tumor to encourage its occurrence and progression. Additionally, it impacts immunosuppressive molecule expression, impacts the tumor microenvironment's immunological and non-immune cell counts and composition, and promotes the growth of a tumor microenvironment that suppresses the immune system. Immunotherapy is a commonly used treatment method nowadays. However, in most patients with cancer, immunotherapy often exhibits low response rates and drug resistance. The secret to increasing the efficacy of tumor immunotherapy is to overcome the tumor microenvironment's immunosuppressive state. In recent years, researchers have developed a number of drugs that target the

To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective case series. In ORN treatment, PENTO/PENTOCLO achieved complete healing in 54% to 100% of patients, with improved symptoms and reduced need for surgery. The addition of clodronate (PENTOCLO) showed mixed results, with 1 large cohort suggesting no additional benefit over PENTO alone. PENTO prophylaxis before dental extractions in irradiated patients resulted in low ORN incidence (0%-5%). In MRONJ, PENTO improved pain, radiographic healing, and mucosal coverage; the only RCT showed significantly-lower relapse rates after surgery with adjunctive PENTO. Across all studies, adverse effects were minimal. PENTO is an effective and well-tolerated therapy for ORN and MRONJ, with emerging evidence supporting its use in prevention protocols. While PENTOCLO may benefit select ORN cases, further trials are needed to define optimal regimens. PENTO offers a noninvasive, accessible alternative to surgery and hyperbaric oxygen therapy. Background and Clinical Significance: Sodium hypochlorite (NaOCl) is widely used in root canal treatment for its potent antiseptic and antibacterial effects. However, its cytotoxicity-particularly at higher concentrations and in patients with low immune status-has been associated with serious postoperative complications. This case report describes the risks associated with NaOCl exposure in a medically compromised patient and reviews the relevant literature on NaOCl-related injuries, offering insights into potential current management strate

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Salvage chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) remains a standard therapy for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who relapse > 1 year after frontline treatment. We evaluated the safety and efficacy of polatuzumab vedotin (Pola) combined with R-ICE salvage chemotherapy, followed by post-ASCT Pola maintenance, aiming to improve complete response (CR) rates and enhance post-ASCT outcomes in r/r DLBCL. Notably, the study's accrual period predated the approvals of second-line CAR T cell therapies. Forty-one patients were enrolled and received PolaR-ICE. Adverse effects of the combination were consistent with those observed with Pola and R-ICE chemotherapy with no new toxicity signals observed and were most commonly hematologic and gastrointestinal. The overall response rate after salvage was 88% with a CR rate of 56%. Twenty-two patients (56%) went on to receive autologous stem cell transplant and 16 (39%) received Pola consolidation. At a median follow-up of 25 months (range: 18-21), the 2-year PFS of all patients treated with PolaR-ICE (n = 41) was 49.9% (95% CI: 31.7-65.7) and 2-year OS was 75.0% (95% CI: 58.5-85.8). Patients with relapse ≤ 12 months of initial therapy achieved a 2-year PFS of 36.4% (90% CI: 17.1-56.0) versus 80.0% (95% CI: 40.9-94.6) among patients with relapse ≥ 12 months. Our findings demonstrate that Pola-RICE is a safe and effective salvage regimen for r/r DLBCL, which can be considered for patients with late relapse or in areas where CAR T access may be limited. Trial Registration: ClinicalTrials.gov identifier: NCT04665765. In recent years, cryoablation has emerged as a minimally invasive, nephron-sparing treatment option for localized renal cell carcinoma. While partial nephrectomy remains the reference standard, percutaneous image-guided cryoablation represents an appealing alternative for elderly and/or morbid patients, providing short recovery times and aiming to preserve renal function to the greatest extent possible.Technically, the procedure relies on cryoprobes (argon/liquid nitrogen) and employes two freeze-thaw cycles. A key advantage is the excellent visualization of the developing "ice ball" on CT or MRI, which allows for real-time assessment of the ablation zone. A pre-procedural percutaneous tumor biopsy is recommended to confirm histology and grade of malignancy.The available evidence is largely based on retrospective cohort and registry data. There is a lack of randomized long-term comparative studies. Overall, high rates of oncologic control have been reported, but there is a tendency towards a higher risk of local recurrence compared with partial nephrectomy, particularly in larger lesions. Standardized follow-up protocols and prospective data are essential to better define indications, refine combination techniques, and assess long-term outcomes. Die Kryoablation hat sich in den letzten Jahren als minimalinvasive, nephronerhaltende Therapieoption beim lokalisierten Nierenzellkarzinom etabliert. Während die partielle Nephrektomie weiterhin Referenzstandard bleibt, bietet die perkutane, bildgesteuerte Kryoablation bei älteren und/oder morbiden Patient*innen eine attraktive Alternative mit kurzer Rekonvaleszenz und dem Ziel maximaler Nierenfunktionsschonung. Technisch basiert das Verfahren auf Kryosonden (Argon/Flüssigstickstoff) mit 2 Gefrier-Tau-Zyklen; ein wesentlicher Vorteil ist die exzellente Visualisierbarkeit des entstehenden „Eisballs“ in CT/MRT zur unmittelbaren Kontrolle der Ablationszone. Eine prätherapeutische perkutane Tumorbiopsie wird empfohlen, um Histologie und Malignitätsgrad zu sichern. Die verfügbare Evidenz stützt sich überwiegend auf retrospektive Kohorten- und Registerdaten; randomisierte Langzeitvergleiche fehlen. Insgesamt werden hohe onkologische Kontrollraten berichtet, allerdings mit einem tendenziell höheren Lokalrezidivrisiko im Vergleich zur partiellen Nephrektomie, insbesondere bei größeren Läsionen. Standardisierte Nachsorgeprotokolle und prospektive Daten sind zentral, um Indikationsgrenzen, Kombinationstechniken und Langzeitergebnisse weiter zu schärfen. We aimed to investigate the time- and intramuscular temperature-dependent changes in neuromuscular function throughout 1 h of cold-water immersion (CWI) at 10°C. It was hypothesized that acute CWI (<30 min) would not affect neuromuscular function due to limited reductions in intramuscular temperature, whereas prolonged CWI (>30 min) would impair muscle contractility by drastically reducing intramuscular temperature. Twelve healthy participants (nine males and three females) partook in a randomized crossover design study involving 1-h CWI at 10°C of their lower leg, with three experimental visits consisting of 1) 1-h CWI at 10°C (CWI-only), 2) nonfatiguing exercise followed by 1-h CWI at 10°C to mimic the use of postexercise CWI (Ex + CWI), and 3) passive muscle preheating followed by 1-h CWI at 10°C (Heat + CWI). Skin temperature, intramuscular temperature, and neuromuscular function were periodically assessed in the dorsiflexors throughout the 1 h of CWI. Decreased peak power was observed after 10 min of CWI, CWI-only (50.3 ± 16.0%, P < 0.05), Ex + CWI (55.0 ± 18.3%, P < 0.05), and Heat + CWI (62.0 ± 16.8%, P < 0.05), whereas maximal isometric torque decreased after ≥30 min of CWI, CWI-only (81.1 ± 9.1%, P < 0.05), Ex + CWI (86.6 ± 14.3%, P < 0.05), and Heat + CWI (88.7 ± 10.0%, P < 0.05). Decreases in M-wave peak-to-peak amplitude, 50-Hz torque, and postactivation potentiation were only evident following prolonged CWI (P < 0.05). These results highlight that peak power is more sensitive to reductions in intramuscular temperature than maximal isometric strength, reflecting a time- and temperature-dependent effect on skeletal muscle function. Understanding the optical scattering properties of cirrus ice particles is crucial for optimizing atmospheric circulation models, improving radiative transfer simulations, and advancing our understanding of global climate change, including the assessment of cirrus cloud thinning geoengineering strategies. However, due to the limited understanding of cirrus microphysics and the enormous diversity of ice crystal geometries, the microphysical scattering characteristics of cirrus clouds remain an active and challenging topic of research. In this work, based on the convex hull construction algorithm, a new geometrical model of ice crystals, to our knowledge, is proposed to investigate the scattering properties of cirrus cloud particles. A program named Mueller matrix of convex polyhedron (MMCP) has been developed. Light scattering matrices involving complete polarization information are calculated in geometric optics approximation for randomly oriented large crystals with random and given convex polyhedron shapes. The proposed model construction method and computational scheme of the light scattering matrix work for any convex polyhedron within the scope of geometrical optics. To illustrate the broad applicability of the proposed ice crystal model, scattering matrices for three ice crystal examples with different geometrical shapes are calculated under a unified computational framework. Diffraction, interference, and absorption are not considered in this work. The calculated results for the classical hexagonal column model show the overall agreement with those reported by other authors. The crystal model and scattering matrix computational framework developed in this study are applicable to radiative transfer simulations and remote sensing d

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 × 3 mm) fabricated from RMGIC and self-cure GIC were randomly assigned to eight groups (n = 10). Monochromatic (Vitra Unique) and nanohybrid (Filtek Z250 XT) composite resins were bonded using either an etch-and-rinse (Adper Single Bond 2) or self-etch (Clearfil SE Bond) adhesive. SBS was measured using a universal testing machine, and failure modes were analyzed. Data were evaluated using three-way ANOVA and Tukey's post-hoc test (p < 0.05). RMGIC demonstrated significantly higher SBS than self-cure GIC (p = 0.006), and the nanohybrid composite resin exhibited higher SBS values than the monochromatic composite resin (p = 0.005). A significant interaction between GIC type and adhesive strategy was observed (p = 0.033), whereby the etch-and-rinse adhesive enhanced bonding to RMGIC but did not significantly improve bonding to self-cure glass ionomer cement. The highest SBS values were observed when RMGIC was bonded using an etch-and-rinse adhesive and restored with a nanohybrid composite resin, whereas the lowest SBS values occurred when self-cure glass ionomer cement was bonded using a self-etch adhesive and restored with a monochromatic composite resin. RMGIC combined with an etch-and-rinse adhesive, particularly when restored with a nanohybrid composite, provided superior immediate bond strength compared with self-cure GIC. These results reflect short-term in vitro performance and do not represent long-term clinical durability. Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI. Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients. IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes. Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI. The objectives of this study are to evaluate, in vitro, the microhardness, sorption, solubility, color stability, and color-matching ability of monochromatic resin composites: Palfique Omnichroma / Tokuyama (Mono1) and Vittra APS Unique / FGM (Mono2) compared with the conventional resin composite: Filtek Z250 XT / Solventum (Conv). For this analysis, ten disc-shaped composite specimens were prepared for each group for the microhardness, sorption, solubility, and color stability tests. To evaluate color-matching ability, 36 tooth specimens were obtained from the buccal/lingual surfaces of human mol

Eyelid sagging is a frequent concern among aging patients, yet achieving noticeable improvement with noninvasive methods remains challenging. This prospective cohort study evaluated the efficacy and safety of high-intensity focused ultrasound (HIFU) for improving upper and lower eyelid sagging. Thirty-four Korean women (aged 31-67 years) with mild to moderate eyelid laxity underwent a single session of HIFU (ULTRAFORMER MPT) using a 2.0-mm, 4-MHz probe, delivering 120 shots to the periocular region. Outcomes were assessed at 12 weeks via a four-point scale rated by blinded clinicians and patients. Eyelid length was measured using standardized photography. Mean eyelid length decreased by 0.94 ± 0.34 mm (p < 0.0001). Clinical improvement was reported by 76 % of patients and recognized by clinicians in 59 % of cases. The mean scores for overall improvement, eyelid tightening, and crow's feet reduction were 2.25 ± 0.3, 2.10 ± 0.4, and 1.95 ± 0.3, respectively. Mild pain and erythema were the only reported side effects, resolving within 3-4 days. HIFU is a safe and effective noninvasive option for improving both upper and lower eyelid sagging, with high patient satisfaction and minimal adverse effects. High-intensity-focused ultrasound (HIFU) has emerged as a noninvasive approach for facial rejuvenation, offering benefits such as collagen synthesis and subcutaneous fat reduction. However, the differential effects of varying HIFU frequencies on specific skin layers remain underexplored. To evaluate the histological effects of different HIFU frequencies and correlate these findings with patient-reported outcomes, thereby optimizing clinical applications. Histological analysis was performed on pig skin treated with HIFU at specific depths (2.0, 3.0, 4.5, and 6.0 mm) using the Ultraformer MPT device. Collagen types I and III, elastin fibers, and fat reduction were assessed using immunohistochemistry, Victoria blue staining, and Oil Red O staining. Additionally, 50 Asian female participants aged 30-60 years with skin laxity underwent HIFU treatment. Clinical outcomes were evaluated using standardized photographs, the Global Aesthetic Improvement Scale (GAIS), and a modified Rosenberg Self-Esteem Scale. Histological analysis revealed increased collagen and elastin fiber synthesis and significant fat reduction post-HIFU. Clinical outcomes corroborated these findings, with 85.3% of participants reporting overall satisfaction and 70.6% noting improvements in facial contouring. Self-esteem assessments indicated a positive psychological impact, with 64.7% of participants expressing enhanced confidence. HIFU treatment at varying frequencies induces significant histological and clinical improvements, demonstrating its efficacy for skin rejuvenation. This study underscores HIFU's dual role in enhancing physical appearance and psychological well-being, supporting its integration into patient-centric aesthetic care. This investigation delves deep into the lifting degree for each area of noninvasive facial rejuvenation through high-intensity focused ultrasound (HIFU). The study meticulously examines the lifting effects of HIFU treatment across seven distinct facial aesthetic-units, using advanced three-dimensional scanner analysis. The study examined a cohort of 50 patients treated with HIFU. Pre- and immediate posttreatment evaluations were conducted using three-dimensional scanner analysis, allowing for precise quantification of lifting effects across seven aesthetic units. Treatment protocols were tailored to leverage five cartridges with micropulsed mode options, optimizing outcomes based on sonographic anatomy. The forehead was lifted by 1.24 mm; crow's feet, 2.25; malar region, 2.46; posterior cheek, 3.40; jowl, 2.90; mandible, 3.09; and neck, 3.53. The forehead showed a lift of 1.24 mm, attributed to the thin tissue requiring a cautious approach to avoid discomfort. A lift of 2.25 mm in the crow's feet area demonstrated the efficacy of HIFU in addressing fine lines and wrinkles. Significant lift of 2.47 mm in the malar region highlights HIFU's effectiveness in addressing mid-face laxity and restoring volume to the cheeks. The most substantial lift of 3.38 mm in the posterior cheek underscores targeted energy application for enhanced lifting and contouring. Notable lifting effect of 2.90 mm in the jowl area benefits sagging along the jawline, refining facial contour. Lift of 3.10 mm in the mandible shows improvement of lower facial laxity, defining the jawline. The highest lift of 3.55 mm in the neck region addresses laxity and sagging for a defined neck profile.

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been largely limited to simulated scenarios, lacking direct performance comparisons with human experts in complex, real-world clinical tasks. To systematically benchmark five state-of-the-art LLMs against senior physiatrists in formulating comprehensive rehabilitation plans for authentic clinical cases, evaluating their utility as clinical decision support tools. We conducted a rigorous, blinded evaluation using 48 authentic cases across six subspecialties. Plans generated by five LLMs (Grok-4, Gemini−2.5-pro, ChatGPT-5-2025-08-07, Deepseek-r1-0528, and Claude-opus-4-20250514) were compared with expert-authored plans. A panel of 6 senior physiatrists evaluated the plans using a multi-dimensional framework covering four key domains: Clinical Applicability and Safety (primary safety endpoint), Scientific Rigor, Individualization, and Clarity. To address the data’s hierarchical structure, we employed Linear Mixed-Effects Models (LMM) with random intercepts for cases and raters, and fixed effects for models and language. Pairwise comparisons were adjusted using the Holm-Bonferroni correction. Quantitative analysis revealed that Grok-4 (mean 4.31) and Gemini−2.5-pro (mean 4.14) significantly outperformed the human benchmark (derived from standardized expert solutions) (mean 3.56; [Formula: see text]). Notably, the open-source Deepseek-r1 (mean 3.69) also achieved a statistically significant advantage over experts ([Formula: see text]). Conversely, human experts scored numerically higher than Claude-opus-4 (mean 3.50), though this difference was not statistically significant ([Formula: see text]). Qualitative analysis further highlighted human experts’ distinct strengths in strategic pathway design and humanistic care. Top-tier LLMs demonstrate capability in generating high-quality, evidence-based plans, positioning them as effective “executors” for drafting preliminary regimens. We propose a human-AI collaboration paradig

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease triggered by repeated inhalation of organic or chemical antigens. Occupational exposures account for approximately 19% of all cases. Early diagnosis, identification of the responsible antigen(s), and immediate avoidance of exposure are crucial to prevent irreversible pulmonary fibrosis. However, HP often remains unrecognized or is misclassified as another respiratory disorder such as asthma, chronic obstructive pulmonary disease (COPD), or idiopathic pulmonary fibrosis. As a result, the causal link between symptoms and workplace exposure is frequently established only in advanced disease stages-or not at all. Such delays may result in chronic respiratory failure, occupational disability, prolonged oxygen therapy, and, in severe cases, lung transplantation. We report four patients in whom HP was ultimately recognized as an occupational disease or recommended for legal recognition in court. At the time of diagnosis, all cases had progressed to advanced, fibrotic HP, rendering both primary and secondary prevention impossible. In each instance, earlier identification of the occupational trigger followed by immediate antigen avoidance could likely have prevented the development of irreversible lung damage. This case series underscores the need for early and comprehensive pulmonary assessment, including detailed occupational history-taking, serologic and radiologic evaluation, and prompt referral to an occupational physician when HP is suspected. Close interdisciplinary collaboration between pulmonologists and occupational medicine specialists is essential to reduce diagnostic latency, prevent progression to end-stage lung disease, and improve clinical and socioeconomic outcomes. The increasing global incidence of Helicobacter pylori-naive gastric cancer (HPnGC) has established it as a clinical entity warranting further study of its diagnosis, pathogenesis, etiologies, classifications, and management. HPnGC Helicobacter pylori-naive gastric cancer (HPnGC) is an emerging and distinct clinical entity, with its relative burden increasing as global efforts for Helicobacter pylori (HP) eradication succeeds. The cancer is linked to specific etiologies such as Epstein-Barr virus, autoimmune gastritis, and certain hereditary cancer predisposition syndromes, and is characterized by more aggressive histological subtypes, unfavorable anatomical locations, advanced stages at diagnosis, and ultimately poorer prognosis compared to its H. pylori-positive counterpart. Diagnosis requires stringent multi-modal confirmation of absent infection. Currently, endoscopic, surgical, and systemic treatments are similar to those for Helicobacter pylori-positive gastric cancer. This review demonstrates wide knowledge gaps and areas requiring further clarification. Accurate diagnosis remains challenging due to the absence of standardized criteria, highlighting the need for a robust diagnostic framework. Furthermore, it is imperative for further research into the different molecular subtypes and carcinogenic mechanisms to identify cost-effective surveillance methods and effective treatment strategies that contribute to the development of a comprehensive and practical clinical guideline. To investigate the effects of sucralfate suspension gel on gastroscopic pathology and inflammatory cytokine levels in patients with Helicobacter pylori (Hp)-positive chronic non-atrophic gastritis. A retrospective analysis was conducted on 80 outpatients treated at Beijing Hospital of Integrated Traditional Chinese and Western Medicine between January 2022 to January 2025. Patients were divided into a control group (n = 40) and an observation group (n = 40). The control group received standard quadruple therapy, while the observation group received additional treatment with sucralfate suspension gel on top of the standard regimen. Clinical outcomes, gastroscopic pathological scores, gastrointestinal hormone levels, inflammatory cytokine levels and incidence of adverse events were compared between the two groups. The observation group demonstrated a significantly higher overall response rate compared with the control group(P< 0.05). Post-treatment gastroscopic pathological scores were significantly lower in the observation group than in the control group(P< 0.05). Levels of gastrointestinal hormones were significantly elevated in the observation group(P< 0.05). Furthermore, post-treatment levels of interleukin-2, matrix metalloproteinase-9 and tumor necrosis factor-α were significantly reduced in the observation group compared with the control group(P< 0.05, respectively). The incidence of adverse events did not differ significantly between the two groups(P> 0.05). The addition of sucralfate suspension gel to standard therapy in the treatment of Hp-positive chronic non-atrophic gastritis yields favorable clinical outcomes. It can significantly improve gastroscopic pathology, reduce inflammatory cytokine levels and enhance gastrointestinal hormone secretion without compromising treatment safety. This project aims to employ high-performance chemical isotope labeling (HP-CIL) liquid chromatography-mass spectrometry (LC-MS) to conduct a metabolomic study on the mechanisms underlying intrinsic and idiosyncratic drug-induced liver injury (DILI). By comparing the metabolic characteristics between these two types of DILI, we seek to identify biomarkers for predicting intrinsic and idiosyncratic DILI using machine learning strategies. Based on the diagnostic criteria outlined in the EASL clinical practice guidelines on drug-induced liver injury, a review published in NEJM, enrolled DILI cases were classified according to the pathogenic mechanism into an intrinsic type (n = 17) and an idiosyncratic type (n = 27). Serum samples were collected from both groups. Metabolomic profiling was performed using high-performance chemical isotope labeling liquid chromatography-mass spectrometry (HP-CIL LC-MS) to identify differentially expressed metabolites between the two groups. Metabolites that showed significance in both univariate and multivariate statistical analyses were selected for further receiver operating characteristic (ROC) analysis. Machine learning approaches were employed to develop diagnostic models for distinguishing intrinsic and idiosyncratic DILI. These models were compared to identify potential biomarkers capable of discriminating between the two types of DILI, and the diagnostic performance of these candidate biomarkers was evaluated. Serum metabolomic profiling identified four differential metabolites that distinguished intrinsic from idiosyncratic DILI through multivariate and univariate statistical analyses, followed by ROC curve analysis and machine learning-based selection. These potential biomarkers included Alanyl-Glycine (level 1),N2-Acetyl-L-Cystathionine (level 2a), Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a), and Isomer 1 of 5-Hydroxyindoleacetic acid (level 2a). ROC analysis using multiple machine learning models yielded area under the curve (AUC) values greater than 0.8 for all models, indicating high diagnostic performance. Under a multivariate regression model, internal cross-validation (CV) within the training set demonstrated robust model tuning and stability, with an AUC of 0.983. Holdout validation further confirmed model reliability with an AUC of 0.935. Metabolic pathway analysis of these metabolites revealed that the most significantly associated pathways affecting intrinsic and idiosyncratic DILI were primarily related to amino acid metabolism, including tryptophan metabolism, tyrosine metabolism, cysteine and methionine metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. This study demonstrates that machine learning-assisted serum metabolomics can effectively characterize currently well-established intrinsic and idiosyncratic drug-induced liver i

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

To investigate the efficacy of micro-plasma radio-frequency (MPRF) in enhancing the healing of infected skin ulcers. This study involved ten patients diagnosed with infected skin ulcers between May and December 2023. Treatments were administered using MPRF every three days until the ulcers healed completely. We assessed microbial infection status, wound healing progression, healing duration, and changes in patient-reported symptoms such as pain and itching. We also monitored for adverse effects, including erythema and blisters, and evaluated scar formation post-healing. Cultures from the wounds of all ten patients became negative after 2-8 MPRF treatments. After 7-15 treatments, over 90% of the ulcers healed, indicating an effective therapeutic outcome. Patients reported no itching or discomfort during treatment, experiencing only transient, mild, and tolerable pain. No cases of erythema, edema, or other skin irritations were observed. Six-month follow-up showed mild scarring in the treated areas, primarily presenting as hyperpigmentation or hypopigmentation. Micro-plasma radio-frequency (MPRF) demonstrates significant potential in promoting the healing of infected skin ulcers. This is evidenced by the rapid bacterial clearance (cultures turning negative after 2-8 treatments) and a high healing rate (>90% after 7-15 treatments) observed in all 10 patients. Furthermore, its ease of operation, convenient application, and favorable safety profile-characterized by transient, mild, and tolerable pain, absence of local skin irritation (e.g., erythema, edema), and mild scar formation (primarily hyper- or hypopigmentation) upon 6-month follow-up-underscore its promise. While these preliminary findings are encouraging, further large-scale clinical studies are warranted to conclusively establish the efficacy and long-term safety of MPRF in wound healing. This study is classified as a case series, as it included only 10 patients and lacked a control group for comparison. Such a study design does not provide high-level evidence of causality; its findings primarily offer descriptive observations and preliminary evidence for future higher-quality research, such as randomized controlled trials. Skin cancer is the most frequently diagnosed form of cancer worldwide. Diagnostic uncertainty can arise when macroscopic or dermoscopic evaluations do not clearly differentiate between benign and malignant lesions. Laser-induced plasma spectroscopy (LIPS), traditionally used in fields like materials science and environmental analysis, has recently gained attention for its applications in human tissue assessment. LIPS works by generating a (micro)plasma when a laser interacts with tissue, producing element-specific light emissions that can be analyzed in real time. In this study, we explored the potential of LIPS to differentiate between benign and malignant skin lesions using the Spectra-Scope® Score (SSS). Our results revealed a clear distinction: benign lesions showed a median SSS of 1.7, while suspicious and malignant lesions had a significantly higher median score of 8.1 (p < 0.001). Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic performance, with an area under the curve (AUC) of 0.82 (p < 0.001). The findings of this preliminary study support the high accuracy of LIPS in identifying malignancy and underscore its promise as a non-invasive, real-time diagnostic aid. Integrating SSS into clinical workflows could enhance the early detection of skin cancer and reduce reliance on invasive diagnostic procedures. However, further validation is needed to fully establish its role in routine dermatological practice. We developed a sensor called the Submerged Plasma for Isotopic Detection and Elemental Resolution (SPIDER) probe, which uses an atmospheric pressure glow discharge below the surface of liquids to excite species in the liquid. Through emission spectroscopy of molten salts, liquid metals, and heavy water, we demonstrated the SPIDER probe's high resolution, accuracy, and versatility. We successfully identified trace concentrations of transition and rare-earth metals in molten salts and detected the isotopic shift of the Hβ→ Dβ emission line. Our analysis revealed unconventional spectral alkali line shapes, indicating two competing excitation modes: film explosion and droplet vaporization. The film explosion mode, characterized by dense plasma, exhibited self-reversal and broadband continuum emission, while the droplet vaporization mode, associated with diffusive plasma, produced narrow-line emissions. By analyzing circuit transients alongside individual plasma events, we observed that film explosions generate higher currents, likely due to a shorter plasma length as the current preferentially flows through the thin liquid layer. Altogether, our results highlight the SPIDER probe's efficacy and flexibility, making it well-suited for online material quantification of liquids in extreme environments. Hydroxyapatite (HA) has become a widely used material for bone grafting and surface modification of titanium-based orthopedic implants due to its excellent biocompatibility. Among various coating techniques, microplasma spraying (MPS) has gained significant industrial relevance. However, the clinical success of HA coatings also depends on their adhesion to the implant substrate. Achieving durable fixation and reliable biological integration of orthopedic implants remains a major challenge due to insufficient coating adhesion and limited osseointegration. This study addresses challenges in dental and orthopedic implantology by evaluating the microstructure, mechanical properties, and biological behavior of bilayer coatings composed of a zirconium (Zr) sublayer and an HA top layer, applied via MPS onto titanium alloy. Surface roughness, porosity, and adhesion were characterized, and pull-off and shear tests were used to assess mechanical performance. In vitro biocompatibility was tested using rat mesenchymal stem cells (MSCs) to model osteointegration. The results showed that the MPS-fabricated Zr-HA bilayer coatings achieved a pull-off strength of 28.0 ± 4.2 MPa and a shear strength of 32.3 ± 3.2 MPa, exceeding standard requirements. Biologically, the HA top layer promoted a 45% increase in MSC proliferation over three days compared to the uncoated titanium substrate. Antibacterial testing also revealed suppression of E. coli growth after 14 h. These findings support the potential of MPS-applied Zr-HA coatings to enhance both the mechanical integrity and biological performance of titanium-based orthopedic implants. To observe the clinical efficacy of microplasma radiofrequency in treating post-traumatic pigmentary deposition using VISIA quantitative analysis, an innovative approach not previously emphasized in microplasma radiofrequency studies. Twenty patients with post-traumatic pigmentary deposition, treated at Cangzhou Central Hospital between July 2022 and December 2022, were selected. Pigmented areas were divided into four regions (A: control; B, C, D: treated with increasing energy parameters). Adverse effects (erythema, edema, micro-crusts, pruritus) were monitored at 2, 4, and 6 weeks post-treatment using CTCAE v5.0 criteria. Pigmentary deposition scores and VISIA parameters (spots, ultraviolet spots, red areas, brown spots) were evaluated. At 2, 4, and 6 weeks, Groups B, C, D showed significant reductions in pigment scores and VISIA parameters vs Group A (P < 0.05), with Group D (highest energy) achieving maximal improvement. Transient mild-moderate erythema (60-100%), edema (40-80%), and micro-crusts (20-60%) occurred in treated groups, resolving spontaneously within 14 days; no severe adverse events were observed. Microplasma radiofrequency significantly improves post-traumatic pigmentary deposition, with energy-dependent efficacy. Despite transient side effects at higher

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Palladium-catalyzed coupling reactions are indispensable tools for carbon-carbon bond formation, yet their optimization and real-time monitoring remain challenging in homogeneous catalytic systems. Herein, we report a multifunctional fluorescent ligand, (E)-N'-((1H-benzo[d][1,2,3]triazol-6-yl)methylene)-4-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)benzohydrazide (BTACB), which integrates palladium coordination, catalytic activity, and intrinsic fluorescence reporting within a single molecular framework. BTACB exhibits strong fluorescence emission at 518 nm and undergoes efficient and selective quenching upon coordination with Pd (II). The BTACB-Pd (II) complex is an effective catalyst for Sonogashira coupling. By combining the in situ fluorescence monitoring system with the Bayesian optimization-random forest model, the optimal reaction conditions can be quickly determined using the time-resolved fluorescence data derived from experiments. Under the optimized conditions, the coupling reaction continued with a yield as high as 99%. It is worth noting that the fluorescence of BTACB is strongly suppressed during the catalytic process and recovers after the reaction is completed, thus achieving continuous, noninvasive, and real-time monitoring of the catalytic process. This work presents a universal strategy in which the catalytically active fluorescent ligand serves as the reaction medium simultaneously. The in situ fluorescence monitoring and machine-learning-assisted optimization data interface provide a new paradigm for the intelligent regulation of palladium catalytic reactions. Chlamydial conjunctivitis accounts for 3 to 30% cases of conjunctivitis of various etiologies. In such patients, latent clinical manifestations do not correspond to morphological changes in the infected organs and tissues. This paper presents the results of a comprehensive examination of a patient with chronic chlamydial conjunctivitis in the setting of a disseminated form of chlamydial infection (DCI). Direct immunofluorescence (DIF) and polymerase chain reaction (PCR) were used for diagnostics. In addition, conjunctival biopsy specimens were obtained for immunohistochemical (IHC) analysis. Chlamydiae were detected in the conjunctiva, in blood and in clinical materials from the urogenital tract using PCR and DIF. IHC analysis showed that Chlamydia trachomatis was detected to a lesser extent in conjunctival epithelial cells and to a greater extent in endothelial cells of the inner lining of capillaries, mainly in the deep sections. Conjunctival biopsy allows obtaining a pathomorphological picture of tissues infected with chlamydia, providing objective confirmation of the etiopathogenetic role of this pathogen in the development of chronic inflammatory processes in the conjunctiva. An important laboratory diagnostic criterion of DCI is the detection of chlamydiae in peripheral blood neutrophils, as well as in endothelial cells of conjunctival capillaries. Хламидийный конъюнктивит составляет от 3 до 30% от числа конъюнктивитов различной этиологии. У таких больных стертые клинические проявления не соответствуют морфологическим изменениям в инфицированных органах и тканях. В данной работе демонстрируются результаты комплексного обследования пациентки с хроническим хламидийным конъюнктивитом на фоне распространенной формы хламидийной инфекции (РФХИ). Для диагностики применяли реакцию прямой иммунофлюоресценции (ПИФ) и полимеразную цепную реакцию (ПЦР). Также был проведен биопсийный забор конъюнктивы для иммуногистохимических (ИГХ) исследований. Методом ПРЦ и ПИФ хламидии были обнаружены в конъюнктиве, крови и клинических материалах из мочеполового тракта. ИГХ-исследование показало, что Chlamydia trachomatis в меньшей степени диагностировалась в эпителиальных клетках конъюнктивы &#

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Injection of Botulinum neurotoxin (BoNT) is regarded as standard treatment for spasmodic dysphonia (SD), reducing the overactivity of the affected muscles. Due to the lack of standardized outcome parameters for diagnosing SD or assessing its treatment over time, the evaluation of systematic clinical evidence on the effects of BoNT therapy on SD symptom control is difficult. The registry presented in this article aimed to evaluate outcomes after BoNT treatment in SD patients in Austria and Germany, based on selected subjective and objective voice parameters. 41 patients with SD were included in this multicentric registry, after drop-out of 2 patients the results of 39/41 (95.1%) patients could be analyzed per protocol. Demographic and treatment characteristics as well as the occurrence of therapy-related side effects were recorded. Perceptual voice sound evaluation (RBH scale), voice range profile measurements (VRP), number of spasms, and severity of voice strain were assessed. Patients were asked to complete the Voice Handicap Index (VHI-9i), the Communicative Participation Item Bank (CPIB), and indicate their perceived phonation effort on a VAS scale. The parameters were compared between baseline and 1-month post-BoNT treatment. The patients received all BoNT type A (Xeomin®/Merz, Allergan®/Allergan or Dysport®/Ipsen). SD symptoms did not affect the frequency or dynamic range of the singing voice nor did they affect MPT; in contrast all the other parameters assessed were aberrant at baseline. BoNT treatment improved Jitter-%, Dysphonia Severity Index (DSI), degrees of roughness and hoarseness, but failed to restore them to normal. BoNT significantly reduced the voice spasm and strain. Phonation effort improved by approximately 50%. VHI-9i classification was reduced from moderate to mild after treatment, and CPIB from moderate to mild. The VHI-9i results were significantly positively correlated with the CPIB results. The results of this registry showed that BoNT injection, the current off-label treatment of SD symptoms, failed to restore normal voice quality. This registry's outcomes also indicate that the choice of the applied BoNT brand is site-specific and does not appear to be associated with differences in efficacy. We also showed that the effects of the BoNT on the SD symptoms are best described by semi-quantitative outcome measures such as spasm counts and voice strain, and by patients-reported outcome measures (PROMs), such as CPIB and VHI-9i than by more objective parameters such as frequency and dynamic range of the singing voice. Background: Cosmetic injection of botulinum neurotoxin type A (BoNT/A) into the submandibular glands is increasingly performed to enhance jawline contour. Although generally considered safe, unintended diffusion of the toxin can impair pharyngeal musculature and lead to dysphagia. Severe aspiration-prone dysphagia after esthetic submandibular gland injection has rarely been described. Case Presentation: A healthy 37-year-old woman developed acute oropharyngeal dysphagia the day after receiving cosmetic contouring injections with incobotulinumtoxinA (Xeomin®), administered to both submandibular glands (20 units per gland, performed without ultrasound guidance). She presented to our rehabilitation medicine clinic 11 days later with severe difficulty swallowing solids and liquids. Her functional oral intake was severely restricted (Functional Oral Intake Scale [FOIS] score 3), and the Eating Assessment Tool-10 (EAT-10) score was 24. Videofluoroscopic swallowing study (VFSS) demonstrated markedly delayed pharyngeal swallow initiation, reduced palatal elevation, poor airway protection, consistent laryngeal penetration, and silent aspiration of thin liquids (Penetration-Aspiration Scale score 8). She underwent diet modification and structured dysphagia rehabilitation. At three months, repeat VFSS showed substantial improvement, with only occasional penetration of large-volume thin liquids, corresponding to FOIS 5 and EAT-10 score 8. By five months, VFSS confirmed complete resolution of penetration and aspiration with normalization of swallowing physiology, reflected by a FOIS score of 7 and EAT-10 score of 1. Conclusions: This case demonstrates that cosmetic incobotulinumtoxinA injection into the submandibular glands, particularly when performed without ultrasound guidance, can lead to significant oropharyngeal dysphagia. Clinicians performing esthetic lower-face procedures should be aware of this potential complication and ensure timely swallowing evaluation and rehabilitation when symptoms arise. Notalgia paresthetica is a condition characterized by pruritus and pain in the upper back, often associated with skin discoloration in the same area. Through Medline, Google Scholar, and Scopus search engines, we identified reports of eight clinical studies (published up to 1 December 2025) on the subject of botulinum neurotoxin therapy for Notalgia Paresthetica (NP). Only one of the eight studies was double-blind and placebo-controlled. The search strategy included only articles published in English and Spanish, and articles providing basic information such as the type of study, type and dose of the toxin, and results of the treatment. Articles not in English or Spanish, review articles, and articles failing basic information were excluded. A total of 34 patients were found across all studies. The injected toxin in the open-label studies was onabotulinumtoxin-A (Botox), whereas in the blinded study, the investigators used incobotulinumtoxinA (Xeomin). All open-label studies reported improvement in pruritus, and some reported improvement in pain, whereas the blinded study failed to do so. The possible reasons for this discrepancy between the blinded and the open-label studies are discussed. There is a need for double-blind, placebo-controlled studies with a larger number of patients, preferably using the same neurotoxin that has suggested efficacy in the open-label studies. The novelty of this review is that it represents a comprehensive and critical literature assessment on this topic and that it includes data not present in the previous reviews of this subject. Trigeminal neuralgia (TN) can be refractory to systemic anticonvulsants. Targeted botulinum toxin type A (BoNT-A) injections are an emerging local therapy. Ultrasound (US) may help identify subclinical peripheral trigger points that are not evident on palpation. We report a case of a 50-year-old male with longstanding left-sided V2-V3 TN who experienced rapid and durable pain relief after US-identified trigger-point mapping, followed by combined intradermal and US-guided intramuscular injections of incobotulinumtoxinA (Xeomin®). On clinical examination, trigger points were not prominent; however, real-time ultrasonography (Clarius L20) identified subtle focal fasciculations/tremor and hyperdynamic areas consistent with peripheral trigger sites. Treatment comprised intradermal "skin-botox" microinjections along the mandibular/zygomatic line (total 20 U; left 15 U, right 5 U) using 34G × 4 mm needles, and US-guided intramuscular masseter injections (total 50 U; 30G × 25 mm needles; higher proportion to symptomatic left side). Pain improved from VAS 8/10 → 2-3/10 within one week and remained reduced for approximately three to four months. No adverse events were observed. The patient also reported aesthetic improvement of jawline contour. US can detect subclinical trigger-point activity and guide precise BoNT-A delivery. Incorporating US-identified trigger-point mapping and US guidance (Clarius L20) allowed targeted intradermal and intramuscular incobotulinumtoxinA injections that produced durable analgesia and cosmetic benefit in refractory TN. Prospective studies should evaluate standardized US-based protocols. Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 Septembe

Microsatellites stability (MSS) colon cancer patients exhibit a significant suppressive immune status, and the functional status of tumor NLRP3 immunosomes plays an important role in regulating the tumor immune microenvironment, but whether they are involved in the regulation of immunosuppression in MSS patients is unclear. Therefore, further exploration of the relevant molecular mechanisms is urgently needed. The Cancer Genome Atlas-Colorectal Cancer (TCGA-COAD) Masked Somatic Mutation data, clinicopathological data were obtained, analyzed, and visualized using the 'maftools' in R package. Tissue microarray (TMA) used for this study includes 100 unselected, non-consecutive, primary, and sporadic CRCs treated between April 2006 and October 2010 in Tianjin Medical University General Hospital and 60 adjacent noncancerous tissues. Demographic and clinicopathological variables were collected, and the clinical value and prognostic impact of NLRP3 expression were analyzed. Tissue immunofluorescence (IF) was applied to investigate the colocalization expression of NLRP3 and ASC in tumor cells. The Vectra 3.0 Automated Quantitative Pathology Imaging System was used to obtain spectral information the NLRP3-ASC colocalization was analyzed by the Fiji Plugin "Coloc2". Cytotoxic T lymphocytes and M2 macrophages in tumor tissue were evaluated by immunohistochemistry. In patients with MSS-CRC, aberrant activation of NLRP3 immunosome was significantly associated with lymph node metastasis of tumors. It is also closely related to the polarization of M2 macrophages in the tumor microenvironment, and further affects the infiltration of CD8+T lymphocytes, thereby creating a suppressive immune microenvironment. Localized scleroderma (LSc) is an autoimmune condition characterized by localized cutaneous sclerosis, sometimes extending into deeper tissues. Phototherapy, including excimer laser therapy (ELT), is considered an effective and minimally invasive treatment option for patients without extracutaneous involvement. However, little is known about the histopathological and molecular alterations that occur during treatment. Here, we report a case of circumscribed morphea successfully treated with ELT, accompanied by detailed longitudinal histological analysis. A 78-year-old woman presented with gradually progressive indurated plaques on both sides of the abdomen. Histopathological examination of the lesional skin revealed dense collagen deposition and perivascular infiltration of lymphocytes, monocytes, and mast cells, confirming the diagnosis of circumscribed morphea. Topical glucocorticoid therapy yielded insufficient improvement, prompting the addition of 308-nm ELT. The patient underwent 12 ELT sessions, administered every two to four weeks with incremental dosing from 100 mJ/cm2 to 240 mJ/cm2, reaching a cumulative dose of 2100 mJ/cm2. This regimen resulted in marked clinical improvement within one year. Post-treatment biopsies demonstrated near-complete resolution of dermal sclerosis, with substantial reductions in inflammatory cell infiltration. Toluidine blue staining and immunohistochemistry further revealed dynamic cellular changes: mast cells and CD3+ T cells were significantly decreased; CD34 expression, absent in lesional dermal mesenchymal cells before treatment, was restored; and α-smooth muscle actin-positive myofibroblasts, abundant at baseline, were markedly reduced following ELT. These findings indicate that ELT not only ameliorates clinical sclerosis but also reverses immune and mesenchymal cell alterations associated with fibrosis. This case highlights the therapeutic potential of ELT in circumscribed morphea and suggests a plausible mechanism by which ELT modulates immune-mesenchymal interactions to attenuate fibrosis in LSc. Although most rhinovirus infections are mild and subside quickly, vulnerable populations may experience severe illness. Identifying populations at risk for severe or complicated rhinovirus illness can strengthen the ongoing search for preventative and therapeutic treatments. This systematic review and meta-analysis aimed to summarize the populations at risk for the development of severe or complicated rhinovirus illness. We searched CENTRAL, EMBASE, and MEDLINE in April 2024 for studies reporting risk factors for severe rhinovirus infection, defined as lower respiratory tract infection (LRTI), hospitalization, critical care unit (CCU) admission, mechanical ventilation, or death. We pooled odds ratios using random-effects meta-analysis, assessed risk of bias using the Newcastle-Ottawa Scale, and rated the certainty of evidence using the GRADE framework. From 29 observational studies (n = 13,185 participants), we analyzed 13 risk factor-outcome combinations. With high certainty, age < 1 year and premature birth are not associated with the risk of LRTI, and diabetes mellitus is not associated with mortality. With moderate certainty, any comorbidity and pulmonary comorbidity are probably associated with increased risk of LRTI, age > 18 years and malignancy are probably associated with increased risk of mortality, and malignancy is probably associated with an increased risk of CCU admission. Many risk factors lacked sufficient evidence for meta-analysis. Individuals with comorbidities are at greater risk of severe rhinovirus illness. Our findings can inform clinical risk stratification and guide the development and targeted use of emerging therapies. Further comprehensive research is required to elucidate additional risk factors and strengthen the evidence. Dental implant failure is influenced by anatomical, systemic, and procedural factors. This study assessed the predictive value of machine learning models: logistic regression, Random Forest, and gradient boosting, using an open-access dataset (Liu et al. 2018) containing demographic, surgical, prosthetic, and systemic variables. Random Forest performed best (accuracy 0.85, ROC-AUC 0.79, F1 = 0.92, recall 0.97), followed by gradient boosting, while logistic regression showed lower sensitivity. Feature importance analysis identified implant location, sinus augmentation, implant dimensions, and patient age as key predictors. Ensemble models and interpretable feature metrics demonstrate strong potential for improving clinical risk stratification in implant dentistry. This study presents a comprehensive phytochemical investigation of the stems of Syringa oblata Lindl., leading to the isolation and structural characterization of fourteen previously undescribed compounds, including ten sesquiterpenoids (oblatiosides H-M and syringanoids A-D) and four lignans (syringalignans A-D). Their structures and absolute configurations were rigorously established through extensive spectroscopic analyses (HR-ESI-MS and 1D/2D NMR) and comparative electronic circular dichroism (ECD) calculations. In bioactivity evaluations, most compounds demonstrated significant inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with syringalignan D (14), oblatioside K (4), and oblatioside I (2) exhibiting the strongest anti-inflammatory effects (IC50 = 12.5 ± 0.79, 15.2 ± 0.98, and 21.1 ± 0.86 µM, respectively), comparable to dexamethasone (IC50 = 35.4 ± 0.39 µM). Additionally, syringalignan B (12) and syringalignan D (14) displayed potent antioxidant activity in the DPPH assay (IC50 = 13.0 ± 0.48 and 22.6 ± 1.12 µM), outperforming several sesquiterpenoids and approaching the activity of ascorbic acid (IC50 = 23.5 ± 0.46 µM). Notably, compound 14 dose-dependently (5-20 µM) suppressed LPS-stimulated ROS generation and lowered IL-6, TNF-α, and IL-1β mRNA levels in RAW264.7 cells, while also markedly reducing phosphorylated P65, JNK, and Erk proteins, indicating potent anti-oxidant and anti-inflammatory activity. These fi

Microsatellites stability (MSS) colon cancer patients exhibit a significant suppressive immune status, and the functional status of tumor NLRP3 immunosomes plays an important role in regulating the tumor immune microenvironment, but whether they are involved in the regulation of immunosuppression in MSS patients is unclear. Therefore, further exploration of the relevant molecular mechanisms is urgently needed. The Cancer Genome Atlas-Colorectal Cancer (TCGA-COAD) Masked Somatic Mutation data, clinicopathological data were obtained, analyzed, and visualized using the 'maftools' in R package. Tissue microarray (TMA) used for this study includes 100 unselected, non-consecutive, primary, and sporadic CRCs treated between April 2006 and October 2010 in Tianjin Medical University General Hospital and 60 adjacent noncancerous tissues. Demographic and clinicopathological variables were collected, and the clinical value and prognostic impact of NLRP3 expression were analyzed. Tissue immunofluorescence (IF) was applied to investigate the colocalization expression of NLRP3 and ASC in tumor cells. The Vectra 3.0 Automated Quantitative Pathology Imaging System was used to obtain spectral information the NLRP3-ASC colocalization was analyzed by the Fiji Plugin "Coloc2". Cytotoxic T lymphocytes and M2 macrophages in tumor tissue were evaluated by immunohistochemistry. In patients with MSS-CRC, aberrant activation of NLRP3 immunosome was significantly associated with lymph node metastasis of tumors. It is also closely related to the polarization of M2 macrophages in the tumor microenvironment, and further affects the infiltration of CD8+T lymphocytes, thereby creating a suppressive immune microenvironment. Localized scleroderma (LSc) is an autoimmune condition characterized by localized cutaneous sclerosis, sometimes extending into deeper tissues. Phototherapy, including excimer laser therapy (ELT), is considered an effective and minimally invasive treatment option for patients without extracutaneous involvement. However, little is known about the histopathological and molecular alterations that occur during treatment. Here, we report a case of circumscribed morphea successfully treated with ELT, accompanied by detailed longitudinal histological analysis. A 78-year-old woman presented with gradually progressive indurated plaques on both sides of the abdomen. Histopathological examination of the lesional skin revealed dense collagen deposition and perivascular infiltration of lymphocytes, monocytes, and mast cells, confirming the diagnosis of circumscribed morphea. Topical glucocorticoid therapy yielded insufficient improvement, prompting the addition of 308-nm ELT. The patient underwent 12 ELT sessions, administered every two to four weeks with incremental dosing from 100 mJ/cm2 to 240 mJ/cm2, reaching a cumulative dose of 2100 mJ/cm2. This regimen resulted in marked clinical improvement within one year. Post-treatment biopsies demonstrated near-complete resolution of dermal sclerosis, with substantial reductions in inflammatory cell infiltration. Toluidine blue staining and immunohistochemistry further revealed dynamic cellular changes: mast cells and CD3+ T cells were significantly decreased; CD34 expression, absent in lesional dermal mesenchymal cells before treatment, was restored; and α-smooth muscle actin-positive myofibroblasts, abundant at baseline, were markedly reduced following ELT. These findings indicate that ELT not only ameliorates clinical sclerosis but also reverses immune and mesenchymal cell alterations associated with fibrosis. This case highlights the therapeutic potential of ELT in circumscribed morphea and suggests a plausible mechanism by which ELT modulates immune-mesenchymal interactions to attenuate fibrosis in LSc. Although most rhinovirus infections are mild and subside quickly, vulnerable populations may experience severe illness. Identifying populations at risk for severe or complicated rhinovirus illness can strengthen the ongoing search for preventative and therapeutic treatments. This systematic review and meta-analysis aimed to summarize the populations at risk for the development of severe or complicated rhinovirus illness. We searched CENTRAL, EMBASE, and MEDLINE in April 2024 for studies reporting risk factors for severe rhinovirus infection, defined as lower respiratory tract infection (LRTI), hospitalization, critical care unit (CCU) admission, mechanical ventilation, or death. We pooled odds ratios using random-effects meta-analysis, assessed risk of bias using the Newcastle-Ottawa Scale, and rated the certainty of evidence using the GRADE framework. From 29 observational studies (n = 13,185 participants), we analyzed 13 risk factor-outcome combinations. With high certainty, age < 1 year and premature birth are not associated with the risk of LRTI, and diabetes mellitus is not associated with mortality. With moderate certainty, any comorbidity and pulmonary comorbidity are probably associated with increased risk of LRTI, age > 18 years and malignancy are probably associated with increased risk of mortality, and malignancy is probably associated with an increased risk of CCU admission. Many risk factors lacked sufficient evidence for meta-analysis. Individuals with comorbidities are at greater risk of severe rhinovirus illness. Our findings can inform clinical risk stratification and guide the development and targeted use of emerging therapies. Further comprehensive research is required to elucidate additional risk factors and strengthen the evidence. Dental implant failure is influenced by anatomical, systemic, and procedural factors. This study assessed the predictive value of machine learning models: logistic regression, Random Forest, and gradient boosting, using an open-access dataset (Liu et al. 2018) containing demographic, surgical, prosthetic, and systemic variables. Random Forest performed best (accuracy 0.85, ROC-AUC 0.79, F1 = 0.92, recall 0.97), followed by gradient boosting, while logistic regression showed lower sensitivity. Feature importance analysis identified implant location, sinus augmentation, implant dimensions, and patient age as key predictors. Ensemble models and interpretable feature metrics demonstrate strong potential for improving clinical risk stratification in implant dentistry. This study presents a comprehensive phytochemical investigation of the stems of Syringa oblata Lindl., leading to the isolation and structural characterization of fourteen previously undescribed compounds, including ten sesquiterpenoids (oblatiosides H-M and syringanoids A-D) and four lignans (syringalignans A-D). Their structures and absolute configurations were rigorously established through extensive spectroscopic analyses (HR-ESI-MS and 1D/2D NMR) and comparative electronic circular dichroism (ECD) calculations. In bioactivity evaluations, most compounds demonstrated significant inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with syringalignan D (14), oblatioside K (4), and oblatioside I (2) exhibiting the strongest anti-inflammatory effects (IC50 = 12.5 ± 0.79, 15.2 ± 0.98, and 21.1 ± 0.86 µM, respectively), comparable to dexamethasone (IC50 = 35.4 ± 0.39 µM). Additionally, syringalignan B (12) and syringalignan D (14) displayed potent antioxidant activity in the DPPH assay (IC50 = 13.0 ± 0.48 and 22.6 ± 1.12 µM), outperforming several sesquiterpenoids and approaching the activity of ascorbic acid (IC50 = 23.5 ± 0.46 µM). Notably, compound 14 dose-dependently (5-20 µM) suppressed LPS-stimulated ROS generation and lowered IL-6, TNF-α, and IL-1β mRNA levels in RAW264.7 cells, while also markedly reducing phosphorylated P65, JNK, and Erk proteins, indicating potent anti-oxidant and anti-inflammatory activity. These fi

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Nurse redeployment is the movement of staff from their usual area of work to another area in response to staff shortage or increased care needs. A primary study examining the experiences of Intensive Care Unit (ICU) nurses reveals negative perceptions and challenges associated with redeployment. This quality improvement study is conducted to address gaps in areas of practice that are little understood and significantly impact patients and staff. This study aims to explore interventions to improve ICU staff experience during redeployment to other clinical areas. Purposive convenience sampling and qualitative interviews were conducted following the implementation of recommended interventions from the primary study. All participants who completed two buddy redeployment shifts were eligible to participate in the interviews. An external qualitative nurse researcher conducted semi-structured interviews. Data were analyzed using an inductive analysis method, and the COREQ guidelines were used for reporting. Data analysis showed major themes of communication challenges, risks, emotional burden, and perspective. The subthemes highlighted the need for better communication due to lack of information clarity and instruction uncertainty, a clear escalation plan to raise issues and concerns, workload imbalance due to task uncertainty, task division, and negative comments, emotional challenges resulting in negative sentiments and staff views that were not considered during the redeployment planning process due to a lack of feedback and suggestions. The findings indicated that though efforts were made to improve the redeployment experience for ICU nursing staff through information and education, the challenges and gaps between an exposure buddy shift to gain a targeted understanding of the ward's workflow, compared to a structured orientation process, are significant. Further research on an orientation process and adequate resourcing before redeploying ICU staff to other units should be conducted and analyzed. Remote photoplethysmography (rPPG) is a non-contact method for measuring physiological parameters using smartphone cameras. While the potential for scalable self-monitoring is promising, little is known about its usability and acceptability among patients with chronic cardiac and respiratory conditions. This qualitative study explored the user experiences of a smartphone-based rPPG app (Vitacam) to assess its usability, acceptability, and perceived utility in real-world conditions. Seven adults with chronic heart or respiratory conditions used the app at home over one week. Semi-structured interviews were conducted and explored using reflexive thematic analysis. Participants appreciated the app's simplicity, real-time guidance, and convenience. Key barriers included environmental sensitivity (e.g. lighting), technical limitations, vague error messaging, and lack of clinical integration. Users valued basic self-monitoring features but expressed concerns about accuracy and interpretation, especially for complex conditions like atrial fibrillation. rPPG via smartphone is a promising, low-burden option for basic self-monitoring in chronic disease management. To increase adoption and utility, future iterations should improve feedback clarity, algorithm sensitivity, and integration with clinical systems. These developments could enhance user trust, accuracy, and long-term engagement. Existing reviews on mental health disparities between deaf and hard-of-hearing (DHH) and hearing populations have focused predominantly on children, adolescents, or older adults, leaving a gap for working-age adults. We conducted a systematic review comparing the prevalence, incidence, and severity of any DSM-5-TR or ICD-11 mental disorder between DHH and hearing adults aged 18-60 years. We aimed to quantify disparities and examine disorder-specific patterns to inform future research, policy, and service development. On 13 December 2025, we searched Ovid Medline, Embase, APA PsycINFO and Web of Science. We included analytical observational studies involving DHH and hearing adults aged 18-60 years, reporting mental disorder prevalence, incidence, or severity. Two researchers independently extracted data, and risk of bias (RoB) was assessed using the modified CLARITY tool. We narratively synthesised findings by aggregating outcomes at the study level using two approaches: summary and majority of the effect directions within a study. Subgroup syntheses examined outcome type, study RoB, age group and mental disorder category. Sixty studies (n = 8 578 466) met inclusion. In the summary-direction synthesis, 58.3% (35/60) of studies reported higher mental disorder outcomes for DHH adults, 21.7% (13/60) found no difference and 20.0% (12/60) had mixed findings; none indicated lower mental disorder outcomes for DHH. Under the majority-direction approach, 65.0% (39/60) showed higher mental disorder outcomes and 35.0% (21/60) no difference. These patterns were consistent across prevalence (62.8-72.1% higher) and severity (61.1% higher). Studies with higher RoB more often reported higher mental disorder outcomes (66.7-72.2%) than lower-RoB studies (54.8-61.9%), though both mirrored the overall synthesis. Effects were similar across younger (61.9-71.4%) and older adult samples (61.1-66.7% higher). Disorder-specific syntheses identified psychotic disorders, post-traumatic stress disorder and suicidal outcomes as having the strongest disparities (≥72.2% higher), followed by general mental disorders, anxiety and depression. Fewer than five studies examined each of the other disorders, thereby limiting conclusions for these disorders. Most available evidence indicates that the prevalence and severity of mental disorders are higher among DHH adults aged 18-60 years than among hearing adults, with limited evidence on incidence. No studies reported lower aggregated mental disorder outcomes for DHH adults. Addressing these disparities requires targeted intervention research, supported by population-based, longitudinal and (quasi-)experimental studies including comprehensive reporting of participant characteristics. This will inform more tailored interventions, improve screening and ultimately contribute to better mental health and quality of life for DHH adults. Aristolochia species have long been used in traditional medicine for their presumed anti-inflammatory, analgesic and antimicrobial properties. However, extensive toxicological and epidemiological evidence now demonstrates that these plants contain aristolochic acids (AAs) I and II, highly potent nephrotoxic, genotoxic, and carcinogenic compounds. This review integrates findings from experimental models, clinical investigations, and environmental monitoring, emphasizing the persistence, mobility, and bioaccumulation of AAs in ecosystems and food chains. Compelling epidemiological data show that exposure to AAs is strongly associated with Balkan endemic nephropathy (BEN) and upper urinary tract carcinoma (UUC), conditions that exhibit some of the highest rates worldwide in regions of sustained environmental contamination. In Taiwan, UUC incidence is globally unmatched and closely linked to chronic ingestion of AA-containing herbal preparations, while in Balkan endemic areas, 30%-45% of individuals affected by BEN develop UUC. In these same regions, AA-derived DNA adducts are detected in the vast majority of exposed populations, serving as highly specific biomarkers of internal dose and demonstrating long-term mutagenic persistence. Environmental exposure levels further support these associations, with AAs detected in contaminated soils, wheat, and corn grains, and a variety of vegetables grown in endemic villages. Root crops in particular accumulate AAs from soil reservoirs influenced by pH-dependent solubility and hydrophobicity, while groundwater in affected areas contains AAs concentrations in the ng/L range, revealing a

Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn's disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development. The presumed link between schizophrenia and creativity has long captured the collective imagination, but empirical data paint a more complex picture: while some patients produce extraordinary artistic works, quantitative studies consistently report lower creativity scores in individuals with schizophrenia compared to healthy controls. This contrasts with phenomenological accounts and clinical observations that highlight the expressive power of language and art in conveying the altered subjective experience of schizophrenia. This study aimed to update the existing evidence on creativity in schizophrenia through a systematic review and meta-analyses, and to assess whether a more fine-grained, ecologically valid approach might offer new insights. A systematic search of major databases yielded 4,043 studies after duplicate removal. Following PRISMA guidelines and strict inclusion criteria, 15 studies were included in the final qualitative synthesis and 13 in the quantitative meta-analyses. Creativity was analyzed both globally and across four subcomponents: elaboration, flexibility, fluency, and originality. Only tasks explicitly designed to elicit creative production were included. All five meta-analyses showed statistically significant deficits in patients with schizophrenia compared to controls. The strongest effects emerged for overall creativity (d = -0.79), fluency (d = -0.83), and originality (d = -0.61). Moderator analyses revealed that age was the only significant variable: older patients showed larger deficits, particularly in fluency and flexibility. Other demographic and methodological factors did not account for variability in outcomes. These findings confirm and extend prior work, suggesting that creativity is broadly impaired in schizophrenia. However, the consistent directionality of the results also raises critical questions about the ecological validity of standardized tests. Phenomenological and qualitative perspectives point to the importance of subjectivity and lived experience-dimensions often diminished by clinical treatments aimed at restoring shared reality. We call for the development of subjectivity-sensitive assessment tools capable of capturing this complexity. Creativity in schizophrenia remains a multidimensional phenomenon that cannot be fully understood through normative psychometric measures alone. Future research should adopt interdisciplinary approaches and develop novel tools for ecological assessment that are more sensitive to the creative potential of individuals with schizophrenia. https://www.crd.york.ac.uk/prospero/, CRD42024629254. [Image: see text] Computer aided detection (CADe) colonoscopy has been shown in randomized controlled trials to improve detection of adenomatous colorectal polyps. However, in real-world settings the benefits are less clear. Our objective was to assess CADe colonoscopy compared to routine colonoscopy in a clinical practice setting in the Arab region with a low screening age (40 years old). After the implementation of the CADe system (GI Genius, Medtronic) in our hospital in September 2021 until July 2023, all CADe cases were registered and matched to routine colonoscopy cases with (1:4) ratio. Assignment of patients to the CADe system versus the routine colonoscopy was pragmatic design based on scheduling and availability factors. Primary endpoints were adenoma per colonoscopy (APC), and adenoma detection rate (ADR). A total of 840 patients were included, out of that 72 patients were excluded due to Boston Bowel Prep <6. The final analysis included 768 patients (161 with CADe, 607 without). The CADe system was found to significantly increase the mean APC (0.602 vs. 0.293; rate ratio 1.80 [1.40–2.32]; P < 0.001) and ADR, 30.4% with CADe versus 16.8% without CADe (adjusted RR 1.68 [1.27–2.22], P < 0.001). There was no significant difference in withdrawal time with CADe. In our study, CADe significantly increased the detection of adenomatous polyps in a young screening age population in a clinical practice setting. These findings support recent randomized controlled trials and contrast the findings of recent studies showing lack of benefit in real world practice. Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynth

Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn's disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development. The presumed link between schizophrenia and creativity has long captured the collective imagination, but empirical data paint a more complex picture: while some patients produce extraordinary artistic works, quantitative studies consistently report lower creativity scores in individuals with schizophrenia compared to healthy controls. This contrasts with phenomenological accounts and clinical observations that highlight the expressive power of language and art in conveying the altered subjective experience of schizophrenia. This study aimed to update the existing evidence on creativity in schizophrenia through a systematic review and meta-analyses, and to assess whether a more fine-grained, ecologically valid approach might offer new insights. A systematic search of major databases yielded 4,043 studies after duplicate removal. Following PRISMA guidelines and strict inclusion criteria, 15 studies were included in the final qualitative synthesis and 13 in the quantitative meta-analyses. Creativity was analyzed both globally and across four subcomponents: elaboration, flexibility, fluency, and originality. Only tasks explicitly designed to elicit creative production were included. All five meta-analyses showed statistically significant deficits in patients with schizophrenia compared to controls. The strongest effects emerged for overall creativity (d = -0.79), fluency (d = -0.83), and originality (d = -0.61). Moderator analyses revealed that age was the only significant variable: older patients showed larger deficits, particularly in fluency and flexibility. Other demographic and methodological factors did not account for variability in outcomes. These findings confirm and extend prior work, suggesting that creativity is broadly impaired in schizophrenia. However, the consistent directionality of the results also raises critical questions about the ecological validity of standardized tests. Phenomenological and qualitative perspectives point to the importance of subjectivity and lived experience-dimensions often diminished by clinical treatments aimed at restoring shared reality. We call for the development of subjectivity-sensitive assessment tools capable of capturing this complexity. Creativity in schizophrenia remains a multidimensional phenomenon that cannot be fully understood through normative psychometric measures alone. Future research should adopt interdisciplinary approaches and develop novel tools for ecological assessment that are more sensitive to the creative potential of individuals with schizophrenia. https://www.crd.york.ac.uk/prospero/, CRD42024629254. [Image: see text] Computer aided detection (CADe) colonoscopy has been shown in randomized controlled trials to improve detection of adenomatous colorectal polyps. However, in real-world settings the benefits are less clear. Our objective was to assess CADe colonoscopy compared to routine colonoscopy in a clinical practice setting in the Arab region with a low screening age (40 years old). After the implementation of the CADe system (GI Genius, Medtronic) in our hospital in September 2021 until July 2023, all CADe cases were registered and matched to routine colonoscopy cases with (1:4) ratio. Assignment of patients to the CADe system versus the routine colonoscopy was pragmatic design based on scheduling and availability factors. Primary endpoints were adenoma per colonoscopy (APC), and adenoma detection rate (ADR). A total of 840 patients were included, out of that 72 patients were excluded due to Boston Bowel Prep <6. The final analysis included 768 patients (161 with CADe, 607 without). The CADe system was found to significantly increase the mean APC (0.602 vs. 0.293; rate ratio 1.80 [1.40–2.32]; P < 0.001) and ADR, 30.4% with CADe versus 16.8% without CADe (adjusted RR 1.68 [1.27–2.22], P < 0.001). There was no significant difference in withdrawal time with CADe. In our study, CADe significantly increased the detection of adenomatous polyps in a young screening age population in a clinical practice setting. These findings support recent randomized controlled trials and contrast the findings of recent studies showing lack of benefit in real world practice. Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynth

Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn's disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development. The presumed link between schizophrenia and creativity has long captured the collective imagination, but empirical data paint a more complex picture: while some patients produce extraordinary artistic works, quantitative studies consistently report lower creativity scores in individuals with schizophrenia compared to healthy controls. This contrasts with phenomenological accounts and clinical observations that highlight the expressive power of language and art in conveying the altered subjective experience of schizophrenia. This study aimed to update the existing evidence on creativity in schizophrenia through a systematic review and meta-analyses, and to assess whether a more fine-grained, ecologically valid approach might offer new insights. A systematic search of major databases yielded 4,043 studies after duplicate removal. Following PRISMA guidelines and strict inclusion criteria, 15 studies were included in the final qualitative synthesis and 13 in the quantitative meta-analyses. Creativity was analyzed both globally and across four subcomponents: elaboration, flexibility, fluency, and originality. Only tasks explicitly designed to elicit creative production were included. All five meta-analyses showed statistically significant deficits in patients with schizophrenia compared to controls. The strongest effects emerged for overall creativity (d = -0.79), fluency (d = -0.83), and originality (d = -0.61). Moderator analyses revealed that age was the only significant variable: older patients showed larger deficits, particularly in fluency and flexibility. Other demographic and methodological factors did not account for variability in outcomes. These findings confirm and extend prior work, suggesting that creativity is broadly impaired in schizophrenia. However, the consistent directionality of the results also raises critical questions about the ecological validity of standardized tests. Phenomenological and qualitative perspectives point to the importance of subjectivity and lived experience-dimensions often diminished by clinical treatments aimed at restoring shared reality. We call for the development of subjectivity-sensitive assessment tools capable of capturing this complexity. Creativity in schizophrenia remains a multidimensional phenomenon that cannot be fully understood through normative psychometric measures alone. Future research should adopt interdisciplinary approaches and develop novel tools for ecological assessment that are more sensitive to the creative potential of individuals with schizophrenia. https://www.crd.york.ac.uk/prospero/, CRD42024629254. [Image: see text] Computer aided detection (CADe) colonoscopy has been shown in randomized controlled trials to improve detection of adenomatous colorectal polyps. However, in real-world settings the benefits are less clear. Our objective was to assess CADe colonoscopy compared to routine colonoscopy in a clinical practice setting in the Arab region with a low screening age (40 years old). After the implementation of the CADe system (GI Genius, Medtronic) in our hospital in September 2021 until July 2023, all CADe cases were registered and matched to routine colonoscopy cases with (1:4) ratio. Assignment of patients to the CADe system versus the routine colonoscopy was pragmatic design based on scheduling and availability factors. Primary endpoints were adenoma per colonoscopy (APC), and adenoma detection rate (ADR). A total of 840 patients were included, out of that 72 patients were excluded due to Boston Bowel Prep <6. The final analysis included 768 patients (161 with CADe, 607 without). The CADe system was found to significantly increase the mean APC (0.602 vs. 0.293; rate ratio 1.80 [1.40–2.32]; P < 0.001) and ADR, 30.4% with CADe versus 16.8% without CADe (adjusted RR 1.68 [1.27–2.22], P < 0.001). There was no significant difference in withdrawal time with CADe. In our study, CADe significantly increased the detection of adenomatous polyps in a young screening age population in a clinical practice setting. These findings support recent randomized controlled trials and contrast the findings of recent studies showing lack of benefit in real world practice. Background: Research on artificial intelligence (AI)-based computer-assisted detection and diagnosis (CADe/CADx) algorithms has focused primarily on digital mammography rather than digital breast tomosynth

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Most fall-prediction models in Parkinson's disease (PD) rely on prior falls, limiting prevention. The Waiting Room of the Future (WROTF) platform collects standardized motor and cognitive measures during routine visits, integrated into electronic health records (EHR). To develop a first-fall prediction model combining WROTF-EHR data and compare its performance with established cognitive- and motor-based models. Previously published motor (Paul) and cognitive (CYCLE-II) models were refit using logistic regression. A new regularized (LASSO) model was developed. All models were evaluated using all participants and only those without prior falls. Among 997 PD patients (mean age 69.6 ± 8.8; 62.8% male; disease duration 3.6 ± 4.3 years), AUCs were 0.77 (Paul), 0.70 (CYCLE-II), and 0.81 (LASSO). In fall-naïve patients, AUCs were 0.62, 0.68, and 0.70. Key predictors included processing speed, walking speed, disease duration, and age. The model enables early fall-risk detection using routinely collected data, supporting proactive and personalized preventive care. The EuroSCOREII risk prediction model is the current gold standard in Europe to predict in-hospital mortality after cardiac surgery and is widely used in clinical decision-making and outcome reporting. A risk prediction model specifically for patients undergoing elective or urgent isolated coronary artery bypass grafting (CABG), a commonly performed cardiac procedure, may lead to a better performance for individual risk prediction. The aim of this study is to validate and refit the EuroSCOREII for 120-day mortality, using international multicentre data from two national quality registries. All elective or urgent isolated CABG procedures performed between 2013 and 2019 in adult patients were included using nationwide data from the Netherlands Heart Registration and SWEDEHEART. The performance of the EuroSCOREII was analyzed in the Dutch cohort, and refitted by estimating a new intercept and coefficient for the linear predictor of the original EuroSCOREII. This refitted model was validated in the Swedish cohort and tested against the original EuroSCOREII model. In total 45,016 procedures from the Netherlands were included for validation and refitting of the model. The refitted model showed similar discrimination to the EuroSCOREII and could be marginally optimized by adding the interaction between age and sex, resulting in a C-statistic of 0.80. This refitted model was validated using 16,374 procedures from the Swedish cohort. The refitted model showed improved calibration and discrimination compared to the original EuroSCOREII. We present a refitted risk prediction model for 120-day mortality after elective or urgent isolated CABG using high-quality nationwide data. Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures. This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA. This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration. Given the elevated rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury (NSSI) in autistic adults, we examined whether autism-informed traits and transdiagnostic personality tendencies jointly relate to these outcomes. One hundred and two adults with clinician-diagnosed autism completed structured clinical interview assessments of lifetime histories of suicidal ideation, attempts, and NSSI. Predictors were six Comprehensive Autistic Trait Inventory (CATI) subscales and selected Personality Inventory for DSM-5 Short Form (PID-5-SF) domains and facets. We fit CATI-only, PID-5 domain, and facet models, then combined significant predictors and refit with age, sex, and IQ as covariates. Shared variance between PID-5-SF facet Anhedonia and CATI Social Interactions showed suppression in joint models, and latent variable modeling confirmed that their shared variance-indexing overlapping reward and social disengagement-was the most consistent correlate of risk across outcomes. PID-5-SF facet Emotional Lability was robustly related to NSSI and to ideation severity. CATI Self-Regulatory Behaviors predicted NSSI. PID-5-SF domain Disinhibition showed no associations. Higher IQ showed a modest protective effect for attempts. Findings highlight central roles of reward-related processes and affective volatility, with added contributions from interpersonal strain and self-regulation. Combining CATI with PID-5 yields complementary targets for assessment and intervention. Key strengths include a clinician-diagnosed autistic sample, a rare direct comparison of people with lifetime suicidal ideation vs. suicide attempts, and an integrated trait framework that moves the field beyond prevalence toward trait-informed risk. Findings support brief screening for anhedonia and emotional lability, autism-adapted behavioral activation, rapid arousal-reduction skills, and attention to social communication needs that may impede disclosure and help-seeking. In 102 clinician‐diagnosed autistic adults, lower enjoyment of daily activities and greater social difficulties were linked to higher risk of suicidal thoughts, suicide attempts, and self‐harm without intent to die. Rapid mood swings als

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Traumatic posterior mediastinal hematoma (TPMH) is a potentially life-threatening entity that, in rare instances, can lead to obstructive shock and sudden death secondary to left atrial compression (LAC). We describe the clinical course and outcomes of seven adult patients with TPMH and LAC. A brief literature review is presented. Seven patients (ages spanning from the 20s to 80s) with TPMH and LAC were identified at a Level 1 trauma center from 2016 to 2023. The first 2 patients were identified following standard quality improvement case reviews for unexplained death. The subsequent five patients were prospectively identified during initial trauma evaluation. A retrospective evaluation of all patients was performed using the chart and computed tomography review. All seven patients sustained polytrauma. The mechanisms of injury were motor vehicle crash (4), motorcycle crash (1), golf cart crash (1), and bicycle crash (1). The first two patients with TPMH and LAC died shortly after admission (167 and 339 min) of suspected obstructive shock without evidence of significant hemorrhage. The subsequent five patients were identified during initial trauma evaluation, and each underwent aggressive fluid resuscitative management with 100% survival. TPMH may lead to significant LAC, which can result in sudden death. Our experience suggests that TPMH with LAC is associated with mid-thoracic spine fractures, rib fractures, and polytrauma secondary to high-energy mechanisms. Emphasis on its early recognition is paramount, with a focus on aggressive fluid and blood resuscitation, vasopressor support when needed, and immediate correction of any coagulopathy. In reviewing the literature, nonoperative management is often successful. Selective cases requiring angiography with embolization or hematoma evacuation via thoracotomy have been documented. Our goal is to raise awareness of this entity and its potential lethality. (J Trauma Acute Care Surg. 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). V. A ganglion cyst is a noncancerous, fluid-filled swelling that usually forms near joints or tendons, with the wrist and hand being the most common locations. These cysts can range in size from small, pea-sized bumps to larger formations similar to the size of a golf ball, and their texture may vary from firm to spongy. Smaller cysts can be asymptomatic and are usually round or spherical in shape. The skin over the cyst may appear stretched and shiny. Ganglion cysts contain a mucoid, gel-like material rich in mucopolysaccharides. Some cysts occur intratendinously, extending deep into the underlying muscle, while others may extend into the carpal bone, causing pain in the wrist or leg. Ganglion cysts that are asymptomatic and do not cause pain typically do not require treatment. This case highlights the occurrence of asymptomatic ganglion cysts in the wrist and leg of a 70-year-old woman, discussing their etiology, theories of formation, clinical features, differential diagnosis, and treatment. We aimed to evaluate the risk factors of ocular complications associated with orbital fractures in a large cohort of patients. In this retrospective study, we analyzed the medical records of 1416 consecutive orbital fracture patients treated at Kyoto Prefectural University of Medicine, Kyoto, Japan between March 2009 and April 2025. Fracture characteristics, causes of injury, and the frequency of ocular complications were assessed via clinical records and associated computed tomography scan images. The factors associated with ocular complications were evaluated with multivariate logistic regression analysis. Ocular complications occurred in 9.5% of the cases, with traumatic mydriasis, hyphema, and commotio retinae being the most common. Multivariate logistic regression identified sports-related injury (OR,2.19; 95% CI, 1.73-2.77, p < .01), male sex (OR,1.51; 95% CI, 1.12-2.03, p < .01), non-trapdoor fracture (OR,1.34; 95% CI, 1.01-1.80, p < .05), combined medial wall and orbital floor fractures (OR,1.32; 95% CI, 1.05-1.67, p = .02) and zygomatic or maxilla bone fracture (OR,1.34; 95% CI, 1.00-1.79, p < .05) as independent predictors of ocular complications. Sports-related injury, particularly those associated with golf and baseball, showed the highest rate of ocular complications, with golf-related orbital fractures resulting in a 100% complication rate and baseball-related orbital fractures resulting in a 38.1% complication rate. Sports-related injuries, male sex, non-trapdoor fractures, combined medial wall and orbital floor fractures and zygomatic or maxilla bone fracture are risk factors for ocular complications. Golf and baseball related orbital fractures are associated with a particularly high incidence of ocular complications, and urgent ophthalmologic examination is warranted in these cases. This study examined associations between driver club head speed (dCHS) and strength, power, and anthropometric measures in elite golfers, analyzed in males and females. Forty-one golfers (22 males, 19 females), including PGA and LPGA Tour professionals, completed a standardized test battery comprising golf swing testing (TrackMan launch monitor), countermovement jump (CMJ), isometric mid-thigh pull (IMTP), isometric bench press (IBP), and trunk rotation power testing. In males, dCHS showed very strong associations with trunk rotation peak power (r = 0.89, 95% confidence intervals [0.72; 0.96]), CMJ impulse and peak power (r = 0.78 [0.53; 0.90]), and IMTP peak force (r = 0.75 [0.47; 0.90]), and a strong association with IBP peak force (r = 0.68 [0.35; 0.86]). In females, dCHS correlated strongly with CMJ impulse (r = 0.67 [0.30; 0.87]), CMJ peak force (r = 0.66 [0.28; 0.86]), IBP peak force (r = 0.60 [0.18; 0.83]), and trunk rotation peak power (r = 0.59 [0.16; 0.82]). Median-split analyses confirmed that high-dCHS golfers consistently outperformed those with lower-dCHS across key strength- and power-related measures, with anthropometric variables further differentiating high- from low-dCHS females. These findings highlight both shared and sex-specific associations of dCHS with physical performance in elite golfers and support the use of CMJ, IMTP, IBP, and trunk rotation power testing for profiling and longitudinal monitoring in this population. This is a case of surgical treatment of a type 4 acromioclavicular (AC) joint separation via an arthroscopically assisted approach and reconstruction with combined suspensory fixation, allograft ligament reconstruction, and suture augmentation. AC joint injuries are relatively common, representing approximately 9% of shoulder injuries and approximately 50% of sport-related shoulder injuries. Most AC joint injuries do well when treated conservatively. However, the literature supports surgical treatment for high-grade injuries, failed conservative treatment, and open injuries or those with threatened soft tissues, with good clinical outcomes. Given the patient's age (14 years), activity level as a multisport high school athlete, limited shoulder function, and type 4 AC joint separation, surgical intervention for AC joint reduction and reconstruction was recommended. The patient is positioned in the beach-chair position. Standard shoulder arthroscopy is performed to evaluate for intra-articular pathology. The rotator interval is opened, and the undersurface of the coracoid is identified and cleared. An incision is created along the distal clavicle in line with the AC joint. The distal clavicle is found tethered in the trapezius muscle and is freed, reduced to its AC joint position, and secured with a K-wire. The AC reconstruction guide is positioned 3 cm medial to the AC joint and hooked under the coracoid base. Using

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Oral mucosal lesions are a common but diagnostically complex clinical challenge in general dental practice, comprising conditions from benign ulcers to potentially malignant disorders and systemic presentations. Early diagnosis and evidence-based management are crucial to prevent complications, including malignant changes. This review provided a practical protocol for the diagnosis and management of oral mucosal lesions for general dental practitioners. Drawing from National Health Service guidelines and retrieved literature via PubMed and Scopus, the findings were synthesized into structured clinical tables outlining diagnostic pathways, first-line and escalated treatment options, and referral criteria. The framework enables classification by clinical appearance and anatomical site, integrating pharmacological therapies with validated herbal agents such as Nigella sativa, honey, chamomile, and Aloe vera for their mucosal healing properties. An emphasis was placed on differentiating clinically similar conditions and addressing neuropathic disorders like burning mouth syndrome with agents such as amitriptyline. The current review advocated for an evidence-based, stepwise approach that enhances diagnostic accuracy, optimizes treatment outcomes, and aids safe, timely referrals in the management of oral mucosal lesions. Non-cirrhotic splanchnic venous thrombosis (SVT) can occur in myeloproliferative neoplasms. We report the case of a 69-year-old man who presented with a 2-week history of epigastric pain and was found to have simultaneous portal, splenic, and superior mesenteric vein thromboses in the absence of cirrhosis or malignancy on contrast-enhanced computed tomography. Laboratory testing revealed elevated haemoglobin/haematocrit with a low-normal mean corpuscular volume (83 fL), biochemical evidence of iron restriction, and an inappropriately low serum erythropoietin level. On further testing, JAK2 V617F was positive, and bone marrow findings supported the diagnosis of polycythemia vera (PV). This presentation is compatible with an iron-deficiency-modified PV phenotype (sometimes referred to as "masked PV"), in which iron restriction can attenuate or obscure typical erythrocytosis, and extensive non-cirrhotic SVT effectively unmasked the underlying clonal disorder. Edoxaban 30 mg once daily (body weight < 60 kg) was initiated without interruption or bleeding, and therapeutic phlebotomy was initiated to control the hematocrit. Follow-up computed tomography on day 78 demonstrated marked thrombus reduction with partial re-opacification of the main portal vein, and the patient continued to have a stable clinical course. This case highlights triple-site, non-cirrhotic SVT as a potential presenting feature of PV and supports early JAK2 V617F and erythropoietin testing, coupled with parallel anticoagulation and PV-directed management, in unexplained non-cirrhotic SVT. Objective: To analyze the mutation characteristics of myeloproliferative neoplasm (MPN) patients with Fanconi anemia (FA) signaling pathway gene mutation. Methods: MPN patients with FA signaling pathway gene mutations (mutation group) diagnosed in the Second Hospital of Tianjin Medical University from September 2017 to October 2024 were retrospectively included. MPN patients without FA signaling pathway gene mutations (non-mutation group) were included by propensity score matching (1∶6 pairing). The patients were followed up to January 31, 2025. The clinical characteristics of the both groups were compared, and the influencing factors of survival time of MPN patients were analyzed by multivariate Cox regression model. Results: There were 22 patients in the mutation group, 8 males and 14 females, with an age [M (Q1, Q3)] of 65 (30, 81) years, including 6, 10 and 6 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively; PV patients had the highest proportion of both BRCA2 and FANCD2 mutations (both are 2/6), ET patients had the highest proportion of BRCA2 mutations (3/10), and PMF patients had the highest proportion of FANCD2 mutations (4/6). There were 132 patients in the non-mutation group, 48 males and 84 females, aged 65 (32, 85) years. The proportions of splenomegaly [45.5% (10/22) vs 14.4% (19/132)], secondary myelofibrosis [27.3% (6/22) vs 9.8% (13/132)], secondary myelodysplastic syndrome (MDS) [4.5% (1/22) vs 0], and secondary acute myeloid leukemia (AML) patients [4.5 (1/22) vs 0] in the mutation group were higher than those in the non-mutation group (all P<0.05); There were no statistica differences in age, sex, initial blood routine hemoglobin, hematocrit, white blood cell count, platelet count, chromosome karyotype abnormalities, thrombosis, secondary cancer, and the proportion of deceased patients between the two groups (all P>0.05). The median follow-up time was 4 (2, 9) years. The 10-year overall survival rate of the mutation group was lower than that of the non-mutation group (82.4% vs 96.2%, P=0.037). FA signaling pathway gene mutation (HR=2.646, 95%CI: 0.316-22.178, P=0.017) was the influencing factor of survival time of MPN patients. Conclusions: The common FA signaling pathway gene mutations in MPN patients are BRCA2, FANCD2; FA signaling pathway gene mutation is an influencing factor for survival of MPN patients. 目的： 分析伴范可尼贫血（FA）信号通路基因突变骨髓增殖性肿瘤（MPN）患者突变特征及预后的影响因素。 方法： 回顾性纳入2017年9月至2024年10月于天津医科大学第二医院诊断为伴FA信号通路基因突变的MPN患者（突变组），使用倾向性评分匹配（1∶6配对）纳入不伴FA信号通路基因突变的MPN患者（非突变组），随访至2025年1月31日，比较2组患者的临床特征，采用多因素Cox回归模型分析MPN患者生存时间的影响因素。 结果： 突变组22例，男8例，女14例，年龄［M（Q1，Q3）］为65（30，81）岁，其中真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）患者分别有6、10和6例；PV患者BRCA2和FANCD2突变比例均最高（均为2/6），ET患者BRCA2突变比例最高（3/10），PMF患者FANCD2突变比例最高（4/6）。非突变组132例，男48例，女84例，年龄65（32，85）岁。突变组脾大［45.5%（10/22）比14.4%（19/132）］、&#x7e

Vaginal flow analysis plays a key role in clinical diagnosis and medical decision-making. Standardizing report formats remains essential to ensure diagnostic reliability. To assess the quality of vaginal smear reporting in five clinical laboratories located in Colombia’s Pacific region. This descriptive, retrospective study examined records from five laboratories (three public, two private) across three cities in the Colombian Pacific region. The evaluation followed the BACOVA ERIGE guidelines to assess the completeness of the analytical components. Researchers used XLSTAT Premium, version 2024, to compute means, standard deviations, proportions, and ratios. They applied the chi square test to compare reporting compliance across laboratories and used multiple correspondence analysis and discriminant analysis to identify reporting patterns and inter-city differences. The study analyzed 1260 records from women aged 18 to 60 years. Of these, 56.8% were pregnant, and 57% were affiliated to the subsidized healthcare system. Compliance with the BACOVA ERIGE guidelines was higher in Ipiales (54.44%) compared to Cali (24.21%) and Quibdó (21.35%) (c², p = 0.047). The multiple correspondence analysis and discriminant analysis identified three distinct reporting profiles by city. The variability in vaginal smear reports underscores the need to standardize post-analytical procedures. Unifying technical criteria among laboratories would improve the diagnostic quality of vaginal flora imbalance and enhance clinical decision-making. El análisis del flujo vaginal cumple un papel clave en el diagnóstico clínico y en la toma de decisiones médicas. La estandarización del informe es esencial para garantizar la confiabilidad diagnóstica. Evaluar la calidad del informe del frotis vaginal de cinco laboratorios clínicos de la región del Pacífico colombiano. Se trata de un estudio descriptivo y retrospectivo basado en los registros de cinco laboratorios (tres públicos y dos privados) ubicados en tres municipios del Pacífico colombiano. Se utilizó la guía BACOVA ERIGE para evaluar si los componentes analíticos estaban completos o incompletos. Los datos se procesaron con XLSTAT Premium, versión 2024, mediante cálculos de medias, desviaciones estándar, proporciones y razones. Se aplicó la prueba de c2 para comparar el cumplimiento entre laboratorios, y se hicieron análisis de correspondencia múltiple y análisis discriminadores para determinar los patrones del informe y las diferencias entre municipios. Se analizaron 1260 registros de mujeres entre los 18 y los 60 años: el 56,8 % estaban embarazadas y el 57 % se encontraban afiliadas al régimen subsidiado. El cumplimiento de la guía BACOVA ERIGE fue mayor en Ipiales (54,44 %) que en Cali (24,21 %) y Quibdó (21,35 %) (c², p = 0,047). Mediante los análisis de correspondencia múltiple y discriminante, se identificaron tres diferentes patrones de informes por municipio. La variabilidad observada en los informes del frotis vaginal pone en evidencia la necesidad de estandarizar los procedimientos posteriores al análisis. La unificación de los criterios técnicos entre laboratorios mejoraría la calidad diagnóstica del desequilibrio de la flora vaginal y fortalecería la toma de decisiones clínicas. The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance. This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS. The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity. 2012-003505-10.

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

This study aims to systematically evaluate the therapeutic effects of the classic Chinese herbal formula Banxia Baizhu Tianma Decoction (BBTD) on a methionine-choline-deficient (MCD) diet-induced mouse model of metabolic dysfunction-associated steatohepatitis (MASH), and to elucidate its underlying mechanisms through multi-omics techniques. The chemical profile of the BBTD water decoction was comprehensively characterized using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). C57BL/6J mice were randomly divided into five groups: normal control group (MCS), model group (MCD), BBTD low-dosage and high-dosage groups (BBTD-L/H), and obeticholic acid (OCA) as a positive control. Therapeutic effect was assessed through biochemistry analysis, histopathological examination of liver (H&E, Oil Red O, Sirius Red staining), and immunohistochemistry analysis. Liver transcriptomics identified key altered pathways, and qRT-PCR and western blotting validated the expression of genes and proteins involved in linoleic acid/arachidonic acid metabolism and the MAPK signaling pathway. Gut microbiota composition was examined by 16S rRNA sequencing along with targeted metabolomic profiling of fecal short-chain fatty acids (SCFAs). Immunofluorescence analysis was used to evaluated the expression of colonic tight junction proteins. A total of 106 compounds were identified from BBTD, spanning more than ten structural classes such as glycosides, flavonoids, organic acids, and triterpenoids. In an MCD diet-induced mouse model of MASH, BBTD administration markedly ameliorated hepatic pathological features. Specifically, it lowered serum levels of ALT, AST, and TBil, lowered hepatic TG content, alleviated hepatocyte steatosis, inflammatory cell infiltration, and collagen deposition. Notably, BBTD exhibited superior anti-fibrotic activity compared to the positive control drug OCA. Mechanistic studies revealed that BBTD exerts hepatoprotective effect via multiple pathways modulation. Transcriptomic analysis demonstrated that BBTD significantly reversed MCD-induced gene expression alternation, with significant enrichment in linoleic acid metabolism and MAPK signaling pathways. Further validation revealed that BBTD not only up-regulated the expression of the fatty acid desaturase FADS2, thereby enhancing the conversion of linoleic acid to γ-linolenic acid, but also re-balanced the arachidonic acid metabolism. This was evidenced by the up-regulation of anti-inflammatory mediators (e.g., EETs, EPA/DHA) and down-regulation of pro-inflammatory mediators (e.g., HETEs), alongside the suppressed expression of COX-2 and ALOX5. Moreover, BBTD dose-dependently inhibited the phosphorylation of key MAPK pathway proteins (p-ERK, p-JNK, p-p38) and down-regulated the downstream early response genes (c-Jun, c-Fos). Regarding intestinal effects, BBTD remodeled the gut microbiota composition, enriching beneficial SCFAs-producing genera such as Faecalibacterium and Roseburia, while reducing pro-inflammatory genera like Turicibacter. Consequently, this shift was accompanied by the increased fecal levels of beneficial SCFAs including butyrate and propionate, enhanced intestinal physical barrier function by up-regulating the expression of colonic tight junction proteins (Occludin, ZO-1, Claudin), and reduced local inflammatory cytokine levels. This study demonstrates that BBTD effectively alleviates MCD-induced MASH in mice via a multicomponent, multitarget mechanism. BBTD simultaneously modulates hepatic and intestinal functions: in the liver, BBTD improves lipid metabolism and suppresses the MAPK-driven inflammatory pathway; in the gut, BBTD remodels the gut microbiota, enhances short-chain fatty acids production, and reinforces the intestinal barrier. From the perspective of the gut-liver axis, this research systematically elucidates that integrated multi-target mechanisms underlying the efficacy of BBTD against MASH and provides a scientific basis for the modernization of traditional Chinese herbal formulae. In implantable collamer lens (ICL) implantation surgery for myopia, achieving a proper vault is a critical hallmark for successful clinical treatment. This study aims to evaluate the performance of two tools in measuring corneal diameter and anterior chamber depth (ACD) for predicting post-ICL implantation vault. The medical records of 213 individuals who underwent ICL implantation were retrospectively reviewed. To minimize selection bias inherent in the two-cohort design, propensity score matching (PSM) was performed, creating a balanced analytical cohort. After matching on key preoperative parameters, 79 matched pairs (Pentacam group: n=79; Sirius group: n=79) were included for all primary analyses. Within this matched cohort, Spearman correlation and ROC curve analyses were used to assess the relationship and diagnostic value of preoperative corneal diameter and ACD with postoperative vault categories (normal, low, high). Based on the propensity score-matched cohorts (n=79 per group), ACD showed a significant positive correlation with postoperative vault in both the Pentacam and Sirius groups, while corneal diameter demonstrated limited and inconsistent correlation. Subgroup analysis revealed that a shallower ACD was associated with low vault in the Pentacam group, while a deeper ACD was related to high vault in both groups. However, the diagnostic value of ACD for predicting abnormal vault was modest and device-dependent, with only the right-eye ACD in the Sirius group presenting a statistically significant area under the curve (AUC). Preoperative ACD is a significant and consistent factor correlated to postoperative ICL vault. Although its absolute predictive performance varied between devices, ACD remained robust biometric parameter available from both the Pentacam and Sirius systems for vault risk assessment. These findings support the clinical utility of ACD in preoperative assessment but highlight the need for device-specific interpretation and further refinement of vault prediction models. Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis. The degree of coincidence and interaction between primary biliary cholangitis (PBC) on the one hand and metabolic syndrome (MetS) or metabolic dysfunction-associated steatotic liver disease (MASLD) on the other is unknown. The aim of the study was to evaluate the associations between MASLD/MetS and PBC, with the focus on liver fibrosis (F). Cross-sectional observational study. Cross-sectional observational study recruited consecutive patients treated for PBC prospectively from a single tertiary center. The con

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Figure/Legend [...]. The aim of this study was to assess the impact of a state-of-the-art 32 cm axial field-of-view GE Omni Legend PET/CT system on administered activity and image quality, and to update Diagnostic Reference Levels (DRLs). System performance was evaluated using NEMA NU 2-2018 measurements and EARL2 accreditation tests. A comparison with the previous 5-ring GE Discovery IQ scanner was performed to analyze the administered activity, scan duration and image quality with and without Artificial Intelligence driven reconstruction. A retrospective analysis of standard-sized adult examinations was conducted to derive updated DRLs values. Omni Legend demonstrated improved sensitivity and Noise Equivalent Count Rate, enabling up to 60% reduction in injected activity while maintaining or improving image quality. Deep learning reconstruction enhanced image quality, particularly at lower administered activities. The DRLs were lower than the national and international reference levels, supporting dose optimization in clinical practice. Understanding heterogeneous patient responses to various glucose-lowering therapies is crucial for advancing personalized treatment approaches and optimizing outcomes for type 2 diabetes mellitus. While average treatment effects are known for many drug classes, patient responses may differ by underlying clinical and demographic factors. We hypothesize that major glucose-lowering drug classes exhibit heterogeneous treatment effects (HTE) across patient subgroups defined by key clinical and demographic characteristics. This is a large-scale observational cohort study replicated in six data-sources across the Observational Health Data Sciences and Informatics network. New-user, active-comparator cohorts were constructed for patients with type 2 diabetes mellitus initiating one of the nine antihyperglycemic drug classes. Large-scale propensity score adjustment for measured confounding, empirical calibration using negative control outcomes, and random-effects meta-analysis were employed to estimate calibrated hazard ratios (HRs). HTE was assessed by comparing differences in log HRs across 10 demographic and clinical subgroups. Evidence of HTE was observed across hyperlipidemia, hypertension, obesity, and sex subgroups. Biguanides (vs. DPP-4i) were protective against acute myocardial infarction in patients with hyperlipidemia, and against heart failure hospitalization in patients with obesity. SGLT-2 inhibitors (vs. GLP-1 receptor agonists) reduced stroke risk only in non-obese patients. Sex-specific patterns also emerged: women taking GLP-1 receptor agonists had a higher risk of diarrhea, and women taking SGLT-2 inhibitors had a lower risk of stroke compared with DPP-4 inhibitors; these associations were not seen for male patients. This hypothesis-generating study identified several potential signals (blood pressure status, lipid status, obesity status, and sex) where there exists treatment effect heterogeneity for several classes of type 2 diabetes mellitus drugs. These preliminary findings highlight the potential for personalized type 2 diabetes mellitus treatment recommendations based on patient characteristics. In CARTITUDE-4, a single infusion of ciltacabtagene autoleucel (cilta-cel) significantly prolonged progression-free survival in patients with lenalidomide-refractory multiple myeloma. We report updated overall survival and longer-term efficacy and safety outcomes. CARTITUDE-4 is an open-label, multicentre, randomised, phase 3 trial at 81 hospital sites in the USA, Europe, Asia, and Australia. Eligible patients were adults (aged >18 years) with lenalidomide-refractory multiple myeloma, with one to three previous treatment lines, including a proteasome inhibitor and an immunomodulatory drug, and an Eastern Cooperative Oncology Group performance status of 0 or 1. After the trial started, the threshold defining measurable disease was lowered to 0·5 g/dL from 1·0 g/dL serum monoclonal paraprotein on July 2, 2021, to increase trial access. Patients were randomly assigned (1:1) via a computerised algorithm and balanced with permuted blocks, with stratification by physician's choice of pomalidomide-bortezomib-dexamethasone versus daratumumab-pomalidomide-dexamethasone, International Staging System stage, and number of previous treatment lines. Patients were assigned to cilta-cel (apheresis, bridging therapy [at least one pomalidomide-bortezomib-dexamethasone or daratumumab-pomalidomide-dexamethasone cycle], lymphodepletion, then cilta-cel infusion [0·75 × 106 CAR T cells per kg]) or standard of care (pomalidomide-bortezomib-dexamethasone [21-day cycles: 4 mg/day oral pomalidomide on days 1-14; 1·3 mg/m2 subcutaneous bortezomib twice a week for 2 weeks for eight cycles, then once a week for 2 weeks per cycle; 20 mg or, if aged >75 years, 10 mg oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 for eight cycles, then days 1, 2, 8, and 9 per cycle] or daratumumab-pomalidomide-dexamethasone [28-day cycles: 1800 mg subcutaneous daratumumab weekly for 2 cycles, every 2 weeks for four cycles, then every 4 weeks; 4 mg/day oral pomalidomide on days 1-21; 40 mg/week or, if aged >75 years, 20 mg/week oral or intravenous dexamethasone]). The primary endpoint was progression-free survival, previously published. In this Article, we report a prespecified second interim analysis of overall survival and an updated analysis of progression-free survival in the intention-to-treat population. This trial was registered at ClinicalTrials.gov (NCT04181827) and is ongoing. Patients were randomly assigned between July 10, 2020, and Nov 17, 2021, to receive cilta-cel (n=208) or standard of care (n=211). At a median follow-up of 33·6 months (IQR 20·3-35·0), median progression-free survival was not reached (95% CI 34·5 months-not evaluable) in the cilta-cel group versus 11·8 months (9·7-14·0) in the standard-of-care group (HR 0·29 [95% CI 0·22-0·39]). Median overall survival was not reached (95% CI not evaluable) with cilta-cel versus not reached (37·7 months-not evaluable) with standard of care (HR 0·55 [95% CI 0·39-0·79]; p=0·0009). 30 (14%) of 208 patients in the cilta-cel group and 77 (37%) of 208 in the standard-of-care group had maximum grade 3 treatment-emergent adverse events, most commonly anaemia (72 [35%]) in the cilta-cel group and neutropenia (59 [28%]) in the standard-of-care group. Rates of maximum grade 4 treatment-emergent adverse events were 156 (75%) with cilta-cel and 116 (56%) with standard of care, most commonly neutropenia (152 [73%] with cilta-cel and 112 [54%] with standard of care). Serious treatment-emergent adverse events occurred in 98 (47%) patients in each group. Deaths in the safety population occurred in 50 (24%) in the cilta-cel group and 82 (39%) in the standard-of-care group, including due to treatment-related adverse events in six (3%; four due to infection) in the cilta-cel group and five (2%; all due to infection) in the standard-of-care group. The significantly improved overall survival and patient-reported measures in CARTITUDE-4 reinforce the use of cilta-cel in treating relapsed or refractory multiple myeloma as early as after first relapse. Johnson & Johnson, Legend Biotech USA. Colonic anastomotic leakage (AL) remains the most severe complication of colorectal surgery, significantly increasing morbidity, mortality, and healthcare burdens. The ideal solution - complete AL prevention without a defunctioning stoma - has long eluded surgeons and patients. Hu et al proposed total enteric flow diversion using a modified ileostomy tube with an inflatable balloon, demonstrating its efficacy in completely preventing AL in porcine models. This innovation echoes the ancient legend of Yu the Great, a Chinese hero renowned for taming the Yellow River's catastrophic floods. Unlike

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Biofilm-associated infections continue to present a formidable clinical challenge, as surface-adhered microbial communities exhibit remarkable tolerance toward conventional antibiotics. Polymeric materials have emerged as a versatile platform for combating biofilms, offering chemical tunability and enabling diverse antimicrobial strategies. This feature review article highlights recent advances in polymeric materials designed to prevent biofilm-associated infections by resisting bacterial adhesion (passive inhibition) or exerting bactericidal effects (active inhibition). These approaches include antifouling surfaces, polymer-nanoparticle composites, and bioinspired materials. Particular attention is given to how polymer structure and functionality (e.g., hydrophobicity, charge, and network architecture) govern bacterial adhesion and viability at interfaces. Emerging glycomaterials are also discussed, where glycan motifs are integrated with nanoparticles or cationic domains to enhance biofilm penetration and antimicrobial efficacy. Collectively, these studies underscore the potential of polymeric materials to modulate microbe-surface interactions, thereby guiding the design of next-generation antibiofilm materials. Not available. Not available. Not available. Not available. Not available. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lat

Although hyaluronic acid-based dermal fillers are widely used, real-world effectiveness and safety data remain limited. To confirm the effectiveness and safety of Belotero Intense and Belotero Intense Lidocaine (cohesive polydensified matrix hyaluronic acid fillers) in a real-world setting. In this multicenter, randomized, rater-blind, uncontrolled, post-market clinical study, 98 participants from 7 sites were randomized 1:1 to Belotero Intense (n = 50) or Belotero Intense Lidocaine (n = 48) (Anteis S.A., Plan-les-Ouates, Switzerland, a company of the Merz Aesthetics group), administered to 2-3 facial areas (nasolabial folds, marionette lines, and upper/lower lips including lip border), with optional touch-up at Week 4. Primary effectiveness endpoints were responder rate (defined as ≥1 point improvement compared with baseline on both sides of the treated area or both lips) at 12 weeks after last injection on the Merz Aesthetics Scales. The responder rate was 85.5% for nasolabial folds (95% confidence interval [CI] 78.4, 92.6; P < .0001), 83.5% for marionette lines (95% CI 75.5, 91.4; P < .0001), and 57.4% for lip volume (95% CI 46.2, 68.7; P = .0967). Post hoc analyses using a revised definition of response for the lips (≥1 point improvement in at least one lip) demonstrated a clinical meaningful improvement (85.1% responder rate; 95% CI 77.0, 93.2). The overall incidence of treatment-related treatment-emergent adverse events was 24.5% and was comparable across the 3 treatment areas. Under real-world conditions, this study demonstrated that Belotero Intense and Belotero Intense Lidocaine were effective and well tolerated in the correction of nasolabial folds, marionette lines and lip volume. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. Hyaluronic acid (HA) fillers are among the most widely used aesthetic treatments, valued for their safety, biocompatibility, and reversibility. Product-specific adverse events (AEs) are important to understand, especially delayed AEs. To evaluate the incidence, severity, and risk factors of AEs following nasolabial fold (NLF) treatment with CPM-B (cohesive polydensified matrix hyaluronic acid filler with 22.5 mg/ml HA; Belotero Balance®; Anteis S.A., Switzerland) across 5 internal clinical studies. Pooled data included treatments to 526 NLFs in 412 patients. Adverse events were categorized into 12 subtypes and rated as mild, moderate, or severe. Multivariable logistic regression was used to evaluate the independent association of patient (age, sex) and procedure-related factors (injection volume, NLF laterality) with AE risk (≥1 vs 0). Adverse events were observed in 41% of treated NLFs; the majority (97%) were mild, with no severe AEs documented. The most common AEs included swelling (23%), erythema (20%), and bruising/ecchymosis (17%). Adverse event risk significantly increased with injection volume; every additional 100 µl raised the odds of an AE by 2.38 (P = .00537). Patient age, sex, and NLF laterality were not significantly associated with AE risk. This study supports the overall safety and tolerability of CPM-B, with most AEs being mild and transient; only 3.8% were moderate, and none were severe. When controlling for study, volume was the only significant predictor of AE risk, highlighting the need for physicians to minimize excessive volumes where possible. Future studies should explore AE predictors in more diverse populations and investigate additional risk factors to optimize safety and outcomes. Aging leads to facial volume loss, particularly in the forehead, resulting in a flat appearance and static wrinkles. Effective forehead rejuvenation aims to restore volume while minimizing risks associated with filler injections. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) fillers are commonly used, with recent interest in hybrid techniques that combine both to optimize aesthetic outcomes. This study evaluates the efficacy and safety of a premixed hybrid filler approach for forehead rejuvenation. A multicenter retrospective cohort study analyzed 111 patients (108 females, 3 males) aged 18-43, who received hybrid injections of CaHA (Radiesse®) and HA (Belotero® Volume) at varying ratios based on forehead contour. The injection volumes and product ratios were customized according to the patients' needs. Follow-ups were conducted at 2 weeks, 3 months, 6 months and 12 months. Primary outcomes were adverse events (AEs) classified per Kadouch criteria; secondary outcomes included patient satisfaction. The cohort consisted of 108 women (97.2%) and 3 men (2.7%), mean age 30.5 years. The average injected volume was 3.11 mL. Two transient minor AEs (1.8%) were reported: localized hematoma and periorbital edema, both resolving with conservative management. No cases of vascular compromise, nodules, migration, or long-term complications were observed. High patient satisfaction was reported across all evaluations. The combination of CaHA and HA fillers administered via a retrograde fanning injection technique in the deep forehead fat plane proved to be both safe and effective in improving frontal depressions, with no adverse events reported during the 12 month observation period. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Despite the widespread use of hyaluronic acid (HA)-based fillers, most studies have focused on volumetric restoration rather than skin quality improvement. Objective imaging techniques, such as ultrasound strain elastography and corneometry, allow quantitative and qualitative assessment of treatment efficacy, filling an important gap in aesthetic dermatology research. To evaluate the safety and efficacy of treatment using the cohesive polydensified matrix hyaluronic acid with glycerol (CPM-R, Belotero Revive; Anteis, Plan-les-Quates, Switzerland) delivered via microcannula for skin hydration, firmness, and elasticity. A retrospective cohort study was conducted, with eligible patients divided into 2 groups: patients who had received a single (group 1) or a two-session treatment (group 2) of CPM-

Poly-L-lactic acid (PLLA) is widely used in aesthetic medicine for its ability to induce neocollagenesis and restore facial volume. Although considered a predictable procedure, technical variability during injection, particularly inconsistent volumetric planning and heterogeneous product distribution, may result in nodules or surface irregularities. This technical report introduces and describes a reusable silicone template designed to assist in volumetric planning for PLLA-SCA (Sculptra; Uppsala, Sweden: Galderma) injections. The BioMold (São Paulo, Brazil: TAB Instrumentos Cirúrgicos Ltd) was developed to support clinicians in performing more structured treatment mapping compared with conventional freehand marking approaches. Rather than relying exclusively on linear retroinjection patterns, the device proposes a spatially organized planning strategy based on predefined geometric sectors. By incorporating commonly adopted reconstitution parameters (10 mL total volume: 8 mL sterile water + 2 mL lidocaine) and the frequently used dose reference of approximately 0.2 mL/cm², the template is intended to help estimate treatment area and injection volume per vector. The device is available in three base sizes (3 cm, 4 cm, and 5 cm), corresponding to volumetric areas of approximately 7.2-12 cm² and suggested injection volumes of 1.4-2.4 mL. Its trapezoidal geometry and integrated slots allow clinicians to transfer retroinjection pathways directly to the skin, which may support more uniform product distribution compared with conceptual mapping techniques. BioMold represents a standardized physical mapping alternative to subjective freehand planning in PLLA procedures. While clinical performance and outcome impact require future investigation, the device is intended to improve planning reproducibility and procedural organization in biostimulatory treatments. Polylactic acid can be classified into poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) according to their stereoisomeric structures, and both are widely used as dermal fillers for soft tissue augmentation. Although the clinical efficacy of commercially available PLLA- and PDLLA-based fillers has been well established, variations in their physicochemical properties may lead to differences in handling characteristics and clinical performance. A systematic comparison of these properties among different PLA-based fillers remains limited. In this study, the physicochemical characteristics of three PDLLA-based fillers (AestheFill, NeoFilera, and Juvelook) and one PLLA-based filler (Sculptra) were evaluated. The analyses included functional group identification, particle morphology and size distribution observation, reconstitution time measurement, osmotic pressure determination, and viscosity assessment. AestheFill and NeoFilera exhibited similar profiles in terms of functional groups, size distribution, osmotic pressure, and viscosity, while NeoFilera and Juvelook showed comparable particle morphologies. Sculptra displayed distinct particle morphology and viscosity, likely attributable to its PLLA composition, yet showed similarities with Juvelook in functional group identification and osmotic pressure. Additionally, the reconstitution times of Sculptra, NeoFilera, and Juvelook were significantly shorter than that of AestheFill. Although the direct correlation between physicochemical characteristics and clinical outcomes warrants further investigation, this comparative analysis provides clinicians with a clearer understanding of the material properties of PLA-based dermal fillers and may assist in the informed selection of appropriate products for individual patients. Poly-L-Lactic acid (Sculptra®, PLLA-SCA®) is a biodegradable bio-stimulating agent composed of irregularly shaped PLLA particles capable of inducing extracellular matrix regeneration. Beyond traditional volumisation, emerging evidence suggests broader epigenetic and adipogenic effects, positioning PLLA as a key agent in regenerative aesthetics. To retrospectively evaluate long-term outcomes of PLLA-SCA treatment in 28 female patients using 3D imaging analysis, focusing on two protocols; (1) full-face skin firming and (2) skin firming with additional targeted volumisation and/or asymmetry correction. A retrospective review of clinical data and standardised 3D stereophotogrammetric imaging was performed two years post-treatment. Patients were divided into the two treatment strategy groups. Volume differences were quantified using validated reconstruction software, and clinical outcomes were assessed through physician evaluation and patient-reported satisfaction. All patients demonstrated measurable soft tissue volume formation at two years, ranging from 0.75cc to 6.4cc per vial of PLLA-SCA. Skin quality improvement and facial harmonisation were consistently observed. No untoward effects, such as vascular compromise, nodules, or granulomas, were reported. PLLA-SCA produces sustained soft-tissue formation and skin firming effects, persisting for at least two years. The findings support PLLA-SCA as an effective regenerative agent with long-lasting volumising and tissue enhancing properties. Delayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics. To develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products. Twenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness. Risk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties. Dermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . To investigate the synergistic effects of Poly-L-Lactic Acid (PLLA) and Retinoic Acid (RA) on age-related skin relaxation in the treatment of facial rejuvenation. 120 patients received facial rejuvenation treatment at Sin-An Cosmetic Clinic Hospital from April 2022 to August 2023 were divided into control group (n=42) and observation group (n=78). Both groups were treated with RA and observation group was added with PLLA. The outer corner wrinkles and lower eyelid wrinkles, nasolabial wrinkles, self-perception ratings of skin effects and adverse reactions incidence were compared between both groups. After treatment, the total improvement rates of outer eye corners, lower eyelid wrinkles and nasolabial folds, the improvement rate of the overall aesthetics of the mid-face, the scores of skin elasticity, water content, skin colour, pores and other skin conditions of t

Chin contouring and projection represent some of the most frequently requested procedures in aesthetic practice using hyaluronic acid (HA) fillers. Variations in the physicochemical and viscoelastic properties of HA fillers may directly influence clinical performance. This study aimed to compare four commercially available HA gels specifically indicated for chin projection: JUVÉDERM® VOLUX, RESTYLANE® LYFT, PERFECTHA® SUBSKIN, and RESTYLANE® SHAYPE. The samples were characterized using scanning electron microscopy, dynamic light scattering, zeta potential, and swelling factor (SF). Rheological assessments included frequency sweep, amplitude sweep, and cohesivity modulus (MOC). All tests were performed in triplicate. JUVÉDERM® VOLUX exhibited the highest SF values (3.28-3.37), indicating greater swelling capacity, whereas RESTYLANE® LYFT showed the lowest (1.53-1.66), reflecting a denser and less expansive profile. Rheological analysis revealed that RESTYLANE® LYFT and RESTYLANE® SHAYPE had higher storage modulus (G') values at elevated frequencies. MOC was significantly higher for RESTYLANE® SHAYPE and PERFECTHA® SUBSKIN compared with JUVÉDERM® VOLUX, suggesting greater resistance to deformation. Overall, RESTYLANE® SHAYPE demonstrated the most favorable balance, combining moderate SF, high G' values, and elevated MOC. However, patient-specific anatomy, aesthetic goals, and injector expertise remain critical in determining the most appropriate product for chin contouring. Hyaluronic acid (HA) dermal fillers are widely used as a non-surgical treatment for facial aging, including nasolabial folds (NLFs). As demand for convenient aesthetic procedures increases, new HA products require rigorous comparison with established fillers. To assess the non-inferiority and safety of a new cross-linked HA filler, SkinPlus-HYAL Implant Lidocaine (test), versus RESTYLANE Lidocaine (control) for temporary correction of moderate to severe NLFs. In this multicenter, randomized, subject- and evaluator-blinded, split-face study, 100 adults with moderate or severe NLFs received the test filler in one NLF and the control in the contralateral NLF. Efficacy was analyzed in the Full Analysis Set (N=93). The primary endpoint was the between-treatment difference in Wrinkle Severity Rating Scale (WSRS) scores at Week 24. Safety was evaluated in the Safety Set (N=100). Group differences were analyzed using a two-sample t-test. At Week 24, mean WSRS scores were 1.85±0.72 (test) and 1.84±0.68 (control). The mean difference (test - control) was 0.01±0.48, with an upper 97.5% one-sided confidence limit of 0.2136, below the prespecified non-inferiority margin of 0.29. Investigator-rated Global Aesthetic Improvement Scale (GAIS) scores at Week 24 and subject-rated GAIS scores at Week 8 favored the test filler. Local adverse event were more frequent with the test (92.00%) than the control (82.0%), but severe injection-site reactions were uncommon, and no serious adverse events occurred. SkinPlus-HYAL Implant Lidocaine was non-inferior to RESTYLANE Lidocaine for correction of moderate to severe NLFs and maintained efficacy through 48 weeks. Despite a higher rate of local reactions, its overall safety profile was acceptable, supporting its use as an effective, safe option for facial aesthetic augmentation. This retrospective study aims to assess the extended efficacy of tear trough hyaluronic acid (TT-HA) filler treatments beyond the commonly reported duration of 6 to 12 months. A retrospective analysis of 155 patients who received TT-HA filler treatments from 2007 to 2023 was conducted. Patient records and photographs were reviewed, and the severity of infraorbital hollowing was graded using the Merz Infraorbital Hollow Assessment Scale (MIHAS). Multivariate regression models were used to analyze factors influencing treatment longevity. Most patients were female (84%) with a mean age of 48 years. Moderate-to-severe infraorbital hollowing was most prevalent at baseline. On average, 0.45mL of filler was injected into each infraorbital hollow using a 27 gauge x 1-inch cannula. Various HA filler products were used, including Belotero Balance®, Juvederm Vollure® XC, Restylane®, and Juvederm Volbella® XC. Most patients experienced an improvement in MIHAS grade posttreatment, with significant results persisting at 18 months. Multivariate regression analysis revealed sustained efficacy over time, with no significant differences in MIHAS grade changes between 6, 12, and 18-month follow-up periods. This study challenges conventional beliefs by demonstrating the extended efficacy of TT-HA fillers, providing evidence of significant improvement in infraorbital hollowing up to 18 months posttreatment. These findings offer valuable insights for clinicians and patients, guiding expectations, and treatment planning in cosmetic dermatology practice. Further research is warranted to elucidate factors contributing to the prolonged longevity of TT-HA fillers to optimize treatment outcomes. The authors sought to evaluate a flexible, hyaluronic acid (HA) filler, Restylane® Defyne™ (HADEF) (Galderma), for combined treatment of chin, nasolabial folds (NLFs), and marionette lines (MLs), in a predefined stepwise order, comparing Down-up (ie, chin first) versus Top-down (NLFs and MLs first) treatment approaches. This postmarketing study complements prior pivotal investigations that demonstrated the safety and effectiveness of HADEF treatments of the lower face, by providing a standardized treatment algorithm for combining several treatment areas in the lower face. HADEF was injected at Day 1 in the first treatment area and at Week 3 in the second area (randomized to either Down-up or Top-down order), with optional touch-up (any area) at Week 6. Assessments included Global Aesthetic Improvement Scale (GAIS), skin firmness, facial harmony, patient satisfaction, and safety until Week 9. Both approaches achieved similar, favorable results at Week 9, with 100% of patients in both groups (Down-up, n=31; Top-down, n=29) demonstrating aesthetic improvement on the GAIS, improved skin firmness and facial harmony, and natural-looking results. Of patients seeking aesthetic improvement of the submental area, 95% in the Top-down group and 100% in the Down-up achieved improvement. Patient-reported endpoints supported these results, with high satisfaction throughout the study. HADEF was well tolerated throughout the study. The results should be considered indicative rather than definitive given the post-marketing design of the study. Both stepwise approaches may be used for administering HADEF when treating the combined areas of chin, NLFs, and MLs. The use of dermal fillers for periocular rejuvenation is common, with hyaluronic acid (HA) being the most popular agent. However, the use of HA in the delicate tear trough region may induce the Tyndall effect, resulting in undesirable bluish discoloration of the lower eyelid. The main drawback of collagen monotherapy is its relatively short effective duration. In this study, FILLDERMTM (manufactured by Jilin Changchun Botai Pharmaceutical Co., Ltd., China) and Restylane® (produced by Galderma SA, Switzerland) were used as the primary treatments. This study evaluated the efficacy and safety of combining collagen with HA for moderate periocular aging. This combination approach was compared with HA and collagen monotherapies. Patients were randomized to receive (1) HA alone, (2) collagen alone, or (3) a combination of HA and collagen via our standardized dual-plane injection protocol (3 sharp-needle periosteal injections + 1 cannula subdermal injection). The treatment outcomes were assessed using the Allergan Infraorbital Hollow Scale (AIHS), the Global Aesthetic Improvement Scale (GAIS), and standardized photographic evaluation at multiple follow-ups. Compared

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

Dronedarone, a multichannel antiarrhythmic drug, was developed as a safer alternative to amiodarone for atrial fibrillation. Although initially considered to have a lower proarrhythmic risk, post-marketing data and clinical experience suggest otherwise. We describe the case of a 44-year-old male with paroxysmal atrial fibrillation and no structural heart disease who developed marked QTc prolongation while receiving dronedarone, despite being asymptomatic. This case highlights the potential for clinically silent but significant QTc prolongation during dronedarone therapy, underscoring the importance of careful ECG monitoring, even in low-risk patients. Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future. Mylabris ("''), derived from the dried bodies of the Chinese blister beetles Mylabris phalerata Pallas and Mylabris cichorii Linnaeus, which has the effect of breaking blood and chasing blood stasis (""), dispersing knots and eliminating symptoms (""), and attacking poison and eroding sores (""). This review provides the firstly comprehensive summary of mylabris, covering its biological characteristics, chemical composition, pharmacological, toxicology, pharmacokinetics, and clinical use. A systematic literature search was conducted in databases ("Web of Science", "PubMed", "Google Scholar", "CNKI", and "WanFang") using the following query ("Mylabris phalerata Pallas" OR "Mylabris cichorii Linnaeus" OR "Mylabris" OR "Banmao" OR "Cantharidin") AND ("Pharmacology" OR "Toxicity" OR "Pharmacokinetics" OR "Marketed drugs"), to identify literature published between 2000 and 2025, focus on referring to 2015-2025. Articles with methodological defects (e.g., sample size less than 5 per group, no standardized purity detection method used), incomplete data (e.g., no access to the original literature, lack of key data values), and ethical problems (no declaration of ethical approval) were excluded. Online websites were also used, including https://ydz.chp.org.cn/#/main (Chinese Pharmacopoeia), https://www.nmpa.gov.cn/datasearch/home-index.html#category=yp (National Medical Products Administration), to obtain information on mylabris- or cantharidin-marketed drugs. Chemical structures in SMILES format were retrieved from the PubChem, and two-dimensional chemical structures were generated using ChemDraw 22.0.0. The major components of mylabris include terpenoids, metallic elements, fatty acids, and peptides. Pharmacological research have demonstrated its anticancer, antithrombotic, and antiviral effects in preclinical study, as well as insecticidal and antifungal in agriculture. Cantharidin is considered to be the main active and toxic component, which can cause gastrointestinal, cardiovascular and respiratory toxicity if used improperly. Pharmacokinetic studies reveal that orally cantharidin predominantly accumulates in the liver and kidneys, exhibiting strong irritancy and low bioavailability. Given its therapeutic efficacy, researchers have also developed various mylabris and cantharidin-based drugs in clinical setting. Mylabris has been used in traditional Chinese medicine for millennia. Now, it treats various diseases and shows development potential. Future studies should focus on four key aspects: comprehensive characterization of active components, elucidation of pharmacological mechanisms, supplementation of pharmacokinetic data, and clarification of toxicological mechanisms. This paper reviews the research progress of mylabris, bridging traditional applications and modern investigations to advance contemporary research and evaluate its therapeutic potential for human diseases. This meta-analysis aimed to evaluate the efficacy of combining CDK4/6i with ET, compared with ET alone, in improving invasive disease-free survival (iDFS), distant recurrence-free survival (DRFS), and overall survival (OS) in early-stage hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer. Given the inconclusive findings of previous meta-analyses, an updated synthesis of the latest phase III trial data was performed. A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized Controlled Trials (RCTs) comparing CDK4/6i plus ET versus ET alone were identified through PubMed, Scopus, and ClinicalTrials.gov. Hazard ratios and adverse events were analyzed using appropriate statistical models. Four RCTs (monarchE, NATALEE, PENELOPE-B, PALLAS) including 17,749 patients were analyzed. CDK4/6 inhibitors improved iDFS (HR 0.80; 95% CI: 0.67-0.96; p = 0.01), while a strong trend toward improved DRFS was observed (HR 0.79; 95% CI: 0.61-1.02; p = 0.07), suggesting a potential clinically relevant benefit that requires longer follow-up to confirm. The effect on OS (HR 0.95; 95% CI: 0.79-1.16; p = 0.63) remains inconclusive. Adverse events, including neutropenia and diarrhea, were more frequent with CDK4/6i. The addition of CDK4/6i to ET improves iDFS and shows a favorable trend in DRFS in early-stage HR+/HER2- breast cancer, highlighting the need for longer follow-up to clarify their long-term benefit. In a preliminary survey study, the authors measured intraocular pressure in the right and left eye of 63 (32 females and 31 bucks) 3-8 month old, clinically healthy European brown hares (Lepus europaeus, Pallas, 1778). The mean intraocular pressure was 25.35 millimeters of mercury (mmHg) (n = 63), 25.4 mmHg for bucks and 25.3 mmHg for females. The average standard deviation was 4.86. The difference in intraocular pressure (IOP) between rabbits aged 3-5 months and 6-8 months was not significant, nor was the difference between females and bucks. In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5-percentage-point lower probability of accepting new Medicare patients (P < 0.001), and hospital or health system-affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring. Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal malignancy that frequently presents with vague or nonspecific symptoms, leading to delayed diagnosis and poor outcomes. Because the small bowel is largely inaccessible to standard endoscopy, many patients endure prolonged abdominal pain, iron deficiency anemia, and weight loss before the underlying pathology is identified. Capsule endoscopy can reveal lesions that are often missed on upper or lower endoscopy and cross-sectional imaging, but its use remains limited in many centers due to issues of availability, cost, or delayed clinical consideration. We report the case of a 79-year-old man with a history of ischemic heart disease and paroxysmal atrial fibrillation who presented with one year of post-prandial abdominal pain, vomiting, and significant weight loss. Initial investigations, including gastroscopy, colonoscopy, and computed tomography of the abdomen and pelvis, were unrevealing. Capsule endoscopy subsequently identified a small bowel mass, and surgical resection confirmed moderately to poorly differentiated adenocarcinoma with negative margins and no nodal involvement. Following surgery, the patient recovered well and remains symptom-free on follow-up imaging. This case highlights the diagnostic challenge of SBA and reinforces the importance of considering capsule endoscopy early in patients with persistent, unexplained gastrointestinal symptoms, especially in elderly individuals with iron deficiency anemia. It also underscores the need for wider access to small bowel imaging in resource-limited settings and calls for further research into optimal post-resection surveillance strategies for small bowel malignancies. This paper presents a model for path-based growing network with preferential attachment motivated by the deployment of quantum key distribution networks. The model is based on a network constructed from path segments of [Formula: see text] nodes on average to mimic real-world quantum key distribution network architectures. Using continuum formalism and the rate equation method, we derive degree exponent, exact degree distributions and demonstrate properties similar to random networks. The theoretical framework incorporates preferential attachment with variable crossover rates and strategic shortcuts, the satellite links. The approach is validated through extensive simulations implemented in Python. Key findings reveal that network robustness, measured by critical fraction for giant component loss, increases with crossover rate and number of satellite links but decreases with segment length. Average distance scales logarithmically with network size, directly impacting secret key consumption during relaying processes in quantum key distribution networks. While preferential attachment enhances connectivity, the model network does not achieve ultra-small world properties of scale-free networks that would minimize key consumption, providing insights for designing cost-effective quantum communication infrastructures. Macroalgae have been used for nutritional and medicinal purposes in many cultures throughout history and they are an important part of traditional diets, especially in Asian countries. This narrative review provides an integrative overview of the effects of bioactive compounds present in brown macroalgae (Phaeophyceae) on nutrition and health. Brown macroalgae are rich in various bioactive compounds such as fucoxanthin, phlorotannin, fucoidan, alginate, and laminarin. These bioactive compounds have antioxidant, anti-inflammatory, antidiabetic, anticancer, and antihypertensive effects and may also exhibit immunoregulating or neuroprotective properties. Macroalgae contain high amounts of protein and polyunsaturated fatty acids, dietary fiber, vitamins, and minerals. Their nutrient contents vary depending on factors such as species, environmental conditions, and harvest time. Pigment and polyphenol derivatives, especially fucoxanthin and phlorotannins, have protective effects against chronic diseases associated with oxidative stress by reducing the effects of free radicals. However, there are very few studies on the bioavailability and mechanisms of the nutrients, phenolics, and flavonoids in macroalgae. Since the metabolic transformations of these metabolites in humans are overlooked, their effects on health are also unclear. More in vivo and clinical studies are needed on the potential use of brown macroalgae in the field of health. Overall, the findings summarized in this narrative review suggest that brown macroalgae represent promising, sustainable, and natural sources of bioactive compounds for future nutritional and health-related applications. Longdan Xiegan decoction (LDXGT), originally documented in the Secret Collection of the Orchid Chamber, is now widely used in clinical practice. While its clinical efficacy against genital herpes (GH) has been established, the underlying therapeutic mechanism remains incompletely understood. This study aims to investigate the mechanism of action of the LDXGT against HSV-2 using genomics, transcriptomics, and real-time quantitative polymerase chain reaction (RT-qPCR). This study presents a UPLC-HRMS and network pharmacology framework for the initial exploration. The optimal potency concentration of LDXGT against HSV-2 infection was determined by cellular assay. Spinal cord neurons from mice model infected with HSV-2 before and after the LDXGT intervention were harvested for a viral genomics analysis. The SH-SY5Y cell model infected with HSV-2 before and after the LDXGT drug-containing serum intervention was obtained for a transcriptomic analysis. Establishing both in vitro and in vivo models with TLR9 overexpression (SH-H9) and knockdown (SH-L9) validated the pathway's role in the antiviral mechanism of LDXGT. RT-qPCR analysis quantified the expression levels of relevant genes. In addition, the LDXGT antiviral efficacy in the HSV-2-infected mouse model was evaluated in combination with the weight, skin lesion index symptom scores and ganglion virus load. Results demonstrated a significant anti-HSV-2 activity of LDXGT in vitro, effectively reducing virus-induced apoptosis. In vivo experiments revealed that LDXGT intervention markedly attenuated body weight loss, skin lesion severity, and decreased the incidence of hind-limb paralysis and mortality in HSV-2-infected mice. Genomics and transcriptomics predicted the anti-HSV-2 efficacy of LDXGT via the TLR9 signaling pathway, and these findings were substantiated by RT-qPCR results from both in vitro and in vivo experiments. The in vivo and in vitro experiments both demonstrated that the LDXGT had significant antiviral efficacy against HSV-2 infection. The present study provided relevant evidence that the LDXGT exerted antiviral efficacy

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with antiresorptive and antiangiogenic treatments commonly prescribed for patients with cancer or osteoporosis. The increasing prescription of these drugs, coupled with the introduction of new anti-cancer medications, has raised concerns regarding the increasing risk of MRONJ. While the precise mechanisms underlying MRONJ remain unclear and effective therapies are still lacking, two repurposed pharmacological protocols-teriparatide (TPTD) and the combination of pentoxifylline (PTX) and α-tocopherol (TOC) [PENTO protocol]-have demonstrated potential therapeutic benefits. However, large-scale clinical evidence remains insufficient. This review evaluates the therapeutic potential of these targeted drug repurposing protocols, exploring their mechanisms of action in MRONJ management and proposing a clinical application protocol for both prevention and treatment. This study also highlights the potential of drug repurposing as a rapid and cost-effective approach for MRONJ management, particularly for patients with cancer, and emphasises the need for further research on personalised and localised management strategies. Nevertheless, the current evidence base is limited by small sample sizes, heterogeneous patient populations, non-randomised study designs, and inconsistent outcome measures, precluding definitive conclusions regarding efficacy and optimal clinical use. To assess the proportion of adverse effects (AEs) associated with the use of PENTO or PENTOCLO protocols for the prevention and management of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A systematic literature search was conducted across six databases (PubMed, Scopus, Embase, Web of Science, LILACS, and Cochrane Library) and gray literature, with no restrictions on date or language. Studies were eligible if they involved adults (≥ 18 years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens. Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%-11.5%; p < 0.1; I2 = 55.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%). The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients. Medication-related osteonecrosis of the jaws (MRONJ) is a complex oral condition for which no global consensus on management currently exists, underscoring the need to establish internationally accepted therapeutic protocols. The use of platelet-rich fibrin (PRF) and the adjunctive administration of pentoxifylline and tocopherol (PenTo) have shown promising preliminary results in the clinical management of MRONJ; however, robust data remain limited. The aim of this study is to analyze the outcomes of surgically treated patients with stage I and II MRONJ, incorporating PenTo as an adjuvant to platelet concentrate therapy. Furthermore, the study seeks to evaluate both clinical and radiographic outcome variables throughout the follow-up period. A controlled pharmacological clinical trial was conducted, using a standard drug regimen as the comparator. Total 20 patients diagnosed with stage I or II MRONJ were allocated into 2 groups: one group received surgical treatment combined with PRF, while the other underwent the same protocol supplemented with an adjuvant therapeutic regimen based on PenTo. Participants were recruited from the Oral Medicine Department, School of Dentistry, Universidad Católica de Córdoba. Statistically significant differences were observed in the mean duration of antiresorptive therapy, which was notably longer in patients with osteoporosis (P = .01). Zoledronic acid was the most frequently associated drug (P = .0019). The addition of PenTo to the treatment protocol was associated with improved clinical and radiographic outcomes, with statistically significant differences (P = .0138 and P = .0046, respectively). Furthermore, the diagnostic stage (I or II) showed a significant correlation with clinical improvement following treatment (P = .0294). The healing index at 15, 90, and 180 days was higher in the group receiving PenTo, with statistically significant differences at each time point (P = .0441; P = .0001; P = .0018, respectively). In oncological patients, the healing index was also higher at all follow-up stages, with clear statistical significance (P = .0294; P = .0004; P = .0042). This study contributes with patient-based evidence to support the interdisciplinary management of MRONJ. The combination of surgical treatment, PRF, and PenTo may serve to optimize and enhance clinical strategies for this condition. Osteoradionecrosis (ORN) is a severe complication of external beam radiation therapy or brachytherapy in patients with head and neck cancer. Traditional theories of its etiology have been unsuccessful in producing a standardized treatment protocol. The theory of radiation-induced fibrosis (RIF) proposes that radiation is responsible for the formation of reactive oxygen species, cytokine production, and constitutive phenotypic expression of myofibroblasts contributing to the development of ORN. The support of the RIF theory in the development of ORN is the basis for the pentoxifylline and tocopherol (PENTO) protocol for the prevention and management of ORN. The authors searched for studies published through April 6, 2025, in the following electronic databases: PubMed, Scopus, Cochrane Library, and ScienceDirect. Peer-reviewed publications were included if they were written in the English language, studied the use of the PENTO protocol, and had "pentoxifylline," "osteoradionecrosis," and "jaw" in their title, abstract, or key words. Sixty-eight articles met the inclusion criteria, 60 of which were included in this scoping review. The authors aimed to describe the pathophysiology of RIF and determine whether the PENTO protocol is effective in the treatment and prevention of ORN of the jaws, thereby warranting further research. The results of this review suggest the PENTO protocol may provide a viable method of both prevention and management of ORN. However, further research is needed to determine the efficacy and safety of the PENTO protocol. The authors emphasized the need for a well-formulated, multidisciplinary, double-blinded, prospective, randomized clinical trial to investigate the use of the PENTO protocol in the prevention and management of ORN of the jaws. Determining the most effective PENTO regimen will maximize patient healing and minimize morbidity. To evaluate the clinical use of pentoxifylline and tocopherol (PENTO), with or without clodronate (PENTOCLO), in the treatment and prevention of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ). A literature review was conducted using PubMed from database inception to May 2025. Studies were included if they evaluated PENTO or PENTOCLO for the treatment or prevention of ORN or MRONJ. Only human studies with full-text availability were included. Data extracted included patient population, intervention details, duration, co-interventions, outcomes, and adverse events. Twenty-two studies met inclusion criteria, comprising randomized trials, prospective cohorts, and retrospective ca

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

Critical limb ischemia (CLI) is limited by the inability of conventional therapies to timely alleviate ischemia-induced inflammatory response and tissue damage. While cell-based therapies have significant potential, their efficacy is constrained by poor cell retention and survival. Inspired by natural extracellular matrix, we developed hierarchical porous microspheres with bionic niche to enhance cell therapy. Small intestinal submucosal decellularized extracellular matrix (SIS-dECM) was selected as the main component, and gelatin methacrylate (GelMA) was introduced to provide suitable mechanical properties and controllable photocrosslinking. An innovative strategy was employed by further introducing polyethylene glycol (PEO) to utilize liquid-liquid phase separation within a dECM-dominated ternary hybrid system, which enabled precise control of the pore and produced interconnected primary macropores (43.3 ± 15.4 μm). Secondary pores were constructed via ice-templating method. Finally, microspheres were modified with fibronectin (FN) to enhance bioactivity. This biomimetic design in biochemical composition, physical structure, and interfacial functionalization enables deep cell infiltration, high cell-loading, and cytoprotection, while maintaining human umbilical cord mesenchymal stem cells (HUMSCs) stemness and enhancing their tri-lineage differentiation potential and paracrine activity. To further promote vascularization, we co-load human umbilical vein endothelial cells (HUVECs) with HUMSCs to form a synergistic system (G-FN@EC/MSC), which demonstrated superior angiogenesis and macrophage M2 polarization in vitro. This treatment achieved high blood flow recovery (94.23% ± 1.42% at day 21) in vivo, with substantial improvement in muscle regeneration and inflammation modulation. This work establishes a new paradigm for fabricating biomimetic microspheres and synergistic cell therapy for CLI. Macrolide resistance genes (erm and mef families) and heavy metal resistance genes (cadA) are increasingly disseminated among streptococci via diverse mobile genetic elements. Through whole-genome sequencing of 16 Streptococcus agalactiae isolates resistant to both erythromycin and clindamycin, we identified 19 integrative and conjugative elements (ICEs), a type of self-transfer genetic elements, conferring antibiotic resistance. Among these, a novel composite ICE designated ICESag39 was identified in S. agalactiae Sag39 through comparative analysis with the NCBI database. ICESag39 measured 113,125 bp in length, and it featured a nested "Russian doll" structure comprising an ICESa2603 family backbone integrated with an internal Tn1806-like ICE. The embedded Tn1806-like ICE contained four variable regions (VR1-VR4) that serve as insertion hotspots; among these, VR3 and VR4 carry erm(TR) from ICESp2907 and the cadmium resistance gene cadA from an uncharacterized genetic element, respectively. Conjugation and excision assays confirmed that ICESag39 transfers at a frequency of 8.2 × 10-9 and co-transfers both resistance determinants. Under cadmium stress, transconjugants carrying ICESag39 displayed enhanced growth relative to the recipient. Although the internal Tn1806-like ICE was also capable of independent transfer, its efficiency was significantly lower (< 10-9), and its circular form is undetectable by PCR. Database screening identified 199 structurally similar ICEs (ICESag39-like ICE), 62.8% (125/199) of which co-carried erm(TR) and cadA, underscoring the prevalence of this ICE and its associated resistance traits. This study characterizes a new composite ICE and elucidates a modular mechanism that facilitates the assembly and dissemination of resistance genes, thereby promoting bacterial genome diversification. Here, we present a protocol for the transformation of Ralstonia solanacearum species complex (RSSC) strains by calcium chloride-induced chemical competence. We include a step-by-step protocol with media and solution recipes, quantitative results of the protocol's efficacy for four of five tested RSSC strains, and an explanation of the logic underlying the protocol development. The protocol involves sequentially treating overnight cultures with a cold calcium chloride solution and a cold calcium chloride/magnesium chloride/glycerol solution, transforming through alternating heat shocks and ice incubations, and recovering cells via an outgrowth in rich medium. Eating disorders are highly prevalent in aesthetic sports, where body weight and physical appearance are central to performance. In figure skating, aesthetic pressure from the competition uniform, along with psychological factors such as perfectionism, anxiety, and self-esteem, may increase the risk of eating disorder. This study examined the relationships between these variables and eating disorder risk among competitive figure skaters, and tested whether self-esteem, aesthetic pressure, and anxiety were indirectly associated with eating disorder risk through perfectionism. Forty-seven Spanish competitive figure skaters (83% female; M = 16.8 years) participated. The CHAD, MPS-F, STAI-R, EAR, and the Uniform Pressure subscale of the WPS-F were administered. Analyses included Spearman correlations, multiple linear regressions, and bootstrapped indirect-effect models. The mean eating disorder risk score was close to the clinical cut-off. Significant positive correlations were found between eating disorder risk, perfectionism, anxiety, and uniform pressure, and a negative correlation with self-esteem. Regression analyses showed that uniform pressure and perfectionism were the strongest predictors of eating disorder risk. Self-esteem, aesthetic pressure and anxiety were indirectly associated to eating disorders risk through perfectionism. Competitive figure skaters exhibit an elevated risk of eating disorders associated with self-demand and aesthetic pressure. Perfectionism emerges as a key cognitive process associated with psychological and social factors, underscoring the potential value of preventive programs focused on managing self-demand and body image perception. However, given the cross-sectional and exploratory nature of the study and the relatively small sample size, these findings should be interpreted with caution. Acute vertigo is among the most frequent causes of access to the Emergency Department. In acute vestibular syndrome, differentiating peripheral from central causes remains challenging. The HINTS protocol provides high diagnostic accuracy but requires expertise and adequately informed physicians. The caloric ice-water test has recently been proposed as a bedside tool to aid this differential diagnosis. This study evaluates a novel approach: simultaneous bilateral ice-water irrigation in association with the HINTS protocol. One hundred consecutive patients presenting with acute vertigo and spontaneous unidirectional nystagmus were enrolled across three Italian centers. All patients underwent clinical assessment including among other the HINTS protocol and the simultaneous bilateral ice-water irrigation. Changes in spontaneous nystagmus during the ice test were recorded. Eighty-six patients fulfilled HINTS criteria for acute unilateral peripheral vestibulopathy, all of whom demonstrated marked suppression/abolition of nystagmus during the simultaneous ice test. In contrast, nystagmus persisted in all 12 patients classified as having central vestibular pathology. Simultaneous bilateral ice-water irrigation is a simple and well-tolerated bedside test that demonstrates strong concordance with the HINTS protocol. While it cannot replace comprehensive clinical assessment, it represents a valuable complementary tool to distinguish peripheral from central causes of acute vertigo. Accurate quantification of chimeric antigen receptor (CAR) T cells is essential for monitoring post-infusion CART expansion and persistence and for

This study investigates adaptive radiotherapy frequency for photon (XT) and proton (PT) treatments of esophageal cancer (EC) patients. We analyzed how adaptation rate is influenced by adaptation criteria and reduced setup error contributions. A database of 18 EC patients with a repeated CT (rCT) after three weeks of treatment was used. Adaptation need was assessed by evaluating clinical goals from the PROTECT trial on the rCT-recalculated doses and comparing them with two dosimetric criteria for iCTV. Robustness was analyzed with reduced setup contributions of 2 mm, 4 mm, and 5 mm. Dosimetric benefits of adaptation were assessed by comparing manually adapted and non-adapted doses. The adaptation rate was strongly affected by the dosimetric threshold and residual setup error. For XT, adaptation frequency decreased from 72% to 33% when residual setup errors were reduced from 5 mm to 2 mm, using iCTV D98% < 96% in the voxelwise minimum dose, the most reported criterion. For PT, rates ranged from 72% to 44% using the same criterion. When applying iCTV V95% < 95% in the worst-case dose (considering all values for the residual setup setting), PT adaptation frequency decreased further to 17%, indicating that employing slightly less conservative criteria could substantially reduce the adaptation rate. Adaptation generally resulted in lower healthy tissue doses and slightly improved target coverage. Discrepancies in adaptation rates highlight the need for consensus guidelines for triggered adaptation in EC, ideally applied with reduced robustness setup settings. AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit. Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation. No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation. This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient. This study aimed to explore the demineralization resistance and remineralization effects of the two newly modulated orthodontic primers and to compare them with those of the Transbond™ XT orthodontic primer. After preparation of graphene oxide/hydroxyapatite (GOHA) and graphite fluoride/bioactive glass (GFBAG) primers, they were evaluated by Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The remineralization properties were evaluated through the assessment of calcium (Ca) and phosphate (PO4) ions released from primer disks (n = 10) for 168 days, the demineralization resistance was explored by evaluating the flat surface of molar teeth (n = 6) by Raman spectroscopy, and the length of the anti-demineralization zone around orthodontic bracket was measured by micro-CT analysis of premolar teeth (n = 5) bonded with one of the experimental or control primers. Both primers showed a homogenous distribution with the presence of Ca in both primers and Fluorine (F) in the GFBAG. High levels of Ca and PO4 ions were reported until the 112th day for the GOHA primer and the 168th day for the GFBAG primer. The result of Raman spectroscopy revealed the maintenance of mineral content with the GFBAG primer, followed by the GOHA primer, after subjecting the teeth to pH cycling to develop WSLs. The micro-CT analysis revealed a significant increase in the anti-demineralization length in both experimental primers compared to the control primer (p < 0.05). The results of the current study collectively illustrate the improvement of the remineralization properties with GOHA and GFBAG primers, with some priority to the GFBAG primer. Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 ×&

This study investigates adaptive radiotherapy frequency for photon (XT) and proton (PT) treatments of esophageal cancer (EC) patients. We analyzed how adaptation rate is influenced by adaptation criteria and reduced setup error contributions. A database of 18 EC patients with a repeated CT (rCT) after three weeks of treatment was used. Adaptation need was assessed by evaluating clinical goals from the PROTECT trial on the rCT-recalculated doses and comparing them with two dosimetric criteria for iCTV. Robustness was analyzed with reduced setup contributions of 2 mm, 4 mm, and 5 mm. Dosimetric benefits of adaptation were assessed by comparing manually adapted and non-adapted doses. The adaptation rate was strongly affected by the dosimetric threshold and residual setup error. For XT, adaptation frequency decreased from 72% to 33% when residual setup errors were reduced from 5 mm to 2 mm, using iCTV D98% < 96% in the voxelwise minimum dose, the most reported criterion. For PT, rates ranged from 72% to 44% using the same criterion. When applying iCTV V95% < 95% in the worst-case dose (considering all values for the residual setup setting), PT adaptation frequency decreased further to 17%, indicating that employing slightly less conservative criteria could substantially reduce the adaptation rate. Adaptation generally resulted in lower healthy tissue doses and slightly improved target coverage. Discrepancies in adaptation rates highlight the need for consensus guidelines for triggered adaptation in EC, ideally applied with reduced robustness setup settings. AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit. Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation. No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation. This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient. This study aimed to explore the demineralization resistance and remineralization effects of the two newly modulated orthodontic primers and to compare them with those of the Transbond™ XT orthodontic primer. After preparation of graphene oxide/hydroxyapatite (GOHA) and graphite fluoride/bioactive glass (GFBAG) primers, they were evaluated by Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The remineralization properties were evaluated through the assessment of calcium (Ca) and phosphate (PO4) ions released from primer disks (n = 10) for 168 days, the demineralization resistance was explored by evaluating the flat surface of molar teeth (n = 6) by Raman spectroscopy, and the length of the anti-demineralization zone around orthodontic bracket was measured by micro-CT analysis of premolar teeth (n = 5) bonded with one of the experimental or control primers. Both primers showed a homogenous distribution with the presence of Ca in both primers and Fluorine (F) in the GFBAG. High levels of Ca and PO4 ions were reported until the 112th day for the GOHA primer and the 168th day for the GFBAG primer. The result of Raman spectroscopy revealed the maintenance of mineral content with the GFBAG primer, followed by the GOHA primer, after subjecting the teeth to pH cycling to develop WSLs. The micro-CT analysis revealed a significant increase in the anti-demineralization length in both experimental primers compared to the control primer (p < 0.05). The results of the current study collectively illustrate the improvement of the remineralization properties with GOHA and GFBAG primers, with some priority to the GFBAG primer. Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 ×&

This study investigates adaptive radiotherapy frequency for photon (XT) and proton (PT) treatments of esophageal cancer (EC) patients. We analyzed how adaptation rate is influenced by adaptation criteria and reduced setup error contributions. A database of 18 EC patients with a repeated CT (rCT) after three weeks of treatment was used. Adaptation need was assessed by evaluating clinical goals from the PROTECT trial on the rCT-recalculated doses and comparing them with two dosimetric criteria for iCTV. Robustness was analyzed with reduced setup contributions of 2 mm, 4 mm, and 5 mm. Dosimetric benefits of adaptation were assessed by comparing manually adapted and non-adapted doses. The adaptation rate was strongly affected by the dosimetric threshold and residual setup error. For XT, adaptation frequency decreased from 72% to 33% when residual setup errors were reduced from 5 mm to 2 mm, using iCTV D98% < 96% in the voxelwise minimum dose, the most reported criterion. For PT, rates ranged from 72% to 44% using the same criterion. When applying iCTV V95% < 95% in the worst-case dose (considering all values for the residual setup setting), PT adaptation frequency decreased further to 17%, indicating that employing slightly less conservative criteria could substantially reduce the adaptation rate. Adaptation generally resulted in lower healthy tissue doses and slightly improved target coverage. Discrepancies in adaptation rates highlight the need for consensus guidelines for triggered adaptation in EC, ideally applied with reduced robustness setup settings. AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit. Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation. No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation. This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient. This study aimed to explore the demineralization resistance and remineralization effects of the two newly modulated orthodontic primers and to compare them with those of the Transbond™ XT orthodontic primer. After preparation of graphene oxide/hydroxyapatite (GOHA) and graphite fluoride/bioactive glass (GFBAG) primers, they were evaluated by Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The remineralization properties were evaluated through the assessment of calcium (Ca) and phosphate (PO4) ions released from primer disks (n = 10) for 168 days, the demineralization resistance was explored by evaluating the flat surface of molar teeth (n = 6) by Raman spectroscopy, and the length of the anti-demineralization zone around orthodontic bracket was measured by micro-CT analysis of premolar teeth (n = 5) bonded with one of the experimental or control primers. Both primers showed a homogenous distribution with the presence of Ca in both primers and Fluorine (F) in the GFBAG. High levels of Ca and PO4 ions were reported until the 112th day for the GOHA primer and the 168th day for the GFBAG primer. The result of Raman spectroscopy revealed the maintenance of mineral content with the GFBAG primer, followed by the GOHA primer, after subjecting the teeth to pH cycling to develop WSLs. The micro-CT analysis revealed a significant increase in the anti-demineralization length in both experimental primers compared to the control primer (p < 0.05). The results of the current study collectively illustrate the improvement of the remineralization properties with GOHA and GFBAG primers, with some priority to the GFBAG primer. Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 ×&

This study investigates adaptive radiotherapy frequency for photon (XT) and proton (PT) treatments of esophageal cancer (EC) patients. We analyzed how adaptation rate is influenced by adaptation criteria and reduced setup error contributions. A database of 18 EC patients with a repeated CT (rCT) after three weeks of treatment was used. Adaptation need was assessed by evaluating clinical goals from the PROTECT trial on the rCT-recalculated doses and comparing them with two dosimetric criteria for iCTV. Robustness was analyzed with reduced setup contributions of 2 mm, 4 mm, and 5 mm. Dosimetric benefits of adaptation were assessed by comparing manually adapted and non-adapted doses. The adaptation rate was strongly affected by the dosimetric threshold and residual setup error. For XT, adaptation frequency decreased from 72% to 33% when residual setup errors were reduced from 5 mm to 2 mm, using iCTV D98% < 96% in the voxelwise minimum dose, the most reported criterion. For PT, rates ranged from 72% to 44% using the same criterion. When applying iCTV V95% < 95% in the worst-case dose (considering all values for the residual setup setting), PT adaptation frequency decreased further to 17%, indicating that employing slightly less conservative criteria could substantially reduce the adaptation rate. Adaptation generally resulted in lower healthy tissue doses and slightly improved target coverage. Discrepancies in adaptation rates highlight the need for consensus guidelines for triggered adaptation in EC, ideally applied with reduced robustness setup settings. AAPM Task Group Report 203 (TG203) recommends implantable cardiac pacemaker (ICP) dependent patients receive elevated precautions and that maximum dose rates to ICPs should be less than 0.2 Gy/min. Unfortunately, there is little quantitative data published about how ICPs are impacted by radiation dose rates near 0.2 Gy/min. The objective of this paper is to report on modern ICP behavior in response to dose rates near this suggested limit. Five single chamber (Azure XT SR) and five dual chamber (Azure XT DR) ICPs were submerged in 0.45% saline solution and placed 1 cm outside the field edge of a 10x10 cm 2 beam. Photon beams of energies 6 MV, 6 FFF, 10 MV, and 10 FFF were tested, with dose rates ranging from 0.15 to 0.92 Gy/min on Varian True Beam and Ethos LINACs. Real-time electrogram data were collected and analyzed for any malfunctions while the beam was on and off. Battery life of each ICP was also checked before irradiation and 6 months post-irradiation. No ICP malfunctions or artifacts were observed, even as dose rate increased. Battery life showed normally expected depletion 6 months post irradiation. This work studies ICP functionality in clinically relevant radiation therapy conditions and measures the performance of the devices in the context of an ICP dependent patient. This study aimed to explore the demineralization resistance and remineralization effects of the two newly modulated orthodontic primers and to compare them with those of the Transbond™ XT orthodontic primer. After preparation of graphene oxide/hydroxyapatite (GOHA) and graphite fluoride/bioactive glass (GFBAG) primers, they were evaluated by Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The remineralization properties were evaluated through the assessment of calcium (Ca) and phosphate (PO4) ions released from primer disks (n = 10) for 168 days, the demineralization resistance was explored by evaluating the flat surface of molar teeth (n = 6) by Raman spectroscopy, and the length of the anti-demineralization zone around orthodontic bracket was measured by micro-CT analysis of premolar teeth (n = 5) bonded with one of the experimental or control primers. Both primers showed a homogenous distribution with the presence of Ca in both primers and Fluorine (F) in the GFBAG. High levels of Ca and PO4 ions were reported until the 112th day for the GOHA primer and the 168th day for the GFBAG primer. The result of Raman spectroscopy revealed the maintenance of mineral content with the GFBAG primer, followed by the GOHA primer, after subjecting the teeth to pH cycling to develop WSLs. The micro-CT analysis revealed a significant increase in the anti-demineralization length in both experimental primers compared to the control primer (p < 0.05). The results of the current study collectively illustrate the improvement of the remineralization properties with GOHA and GFBAG primers, with some priority to the GFBAG primer. Monolithic zirconia has gained widespread use in prosthetic dentistry due to its superior mechanical properties and aesthetics. However, variations in yttria content affect its fracture resistance, especially after artificial aging, which simulates long-term clinical performance. Thirty zirconia crowns were fabricated using Cercon-ht (3% Y-TZP), Cercon-xt ML (5% Y-TZP), and Nexzrr-T multi (3% and 5% Y-TZP). Crowns were cemented onto acrylic dies with GIC luting cement and subjected to artificial aging in a steam autoclave (134°C, 0.2 MPa, five hours). Fracture resistance was tested using a universal testing machine, and data were statistically analyzed. Cercon-ht (3% Y-TZP) showed the highest fracture resistance (6178.00 ± 114.39 N), followed by Nexzrr-T multi (3571.00 ± 171.62 N) and Cercon-xt ML (2178.00 ± 546.70 N). The differences were statistically significant (P < 0.001). Zirconia with lower yttria content (3% Y-TZP) exhibited superior fracture resistance. Multilayer zirconia (3% and 5% Y-TZP) provided a balance between strength and aesthetics, making it a promising alternative for dental restorations. Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic stenosis. However, long-term data exceeding 10 years remain scarce. This study aimed to evaluate long-term clinical outcomes and transcatheter heart valve durability in patients who underwent TAVI and completed a 10-year follow-up. Using data from the multicenter registry in Japan, we analyzed outcomes of 297 patients who received the SAPIEN XT valve (Edwards Lifesciences) from June 2010 to June 2014. All-cause mortality was the primary endpoint. Valve-related outcomes, including bioprosthetic valve failure, were defined according to the Valve Academic Research Consortium 3 criteria. The mean age of the participants was 83.8 ± 6.0 years, and the mean Society of Thoracic Surgeons risk score was 7.5 ± 4.0. Freedom from all-cause mortality at 10 years was 13.2%. Severe structural valve deterioration and bioprosthetic valve failure gradually increased up to 10 years, reaching 3.0% and 10.8%, respectively. Reintervention was performed in 4.5% of patients. Valve-related deaths accounted for 1.3% of all deaths. Most deaths were due to non-valve-related causes. Multivariate analysis revealed that high Society of Thoracic Surgeons score, high clinically frailty scale, renal dysfunction, and low serum albumin levels were independent predictors of mortality. Few older adult high-risk patients survived beyond 10 years following TAVI. In contrast, transcatheter heart valve demonstrated acceptable durability, and long-term outcomes were primarily determined by baseline comorbidities rather than valve dysfunction. These results support the role of TAVI as a feasible therapeutic approach in this population. The bilayered (sandwich) technique combines the biological benefits of glass ionomer cements (GICs) with the esthetics and mechanical strength of composite resins. Interfacial bonding in this technique is influenced by GIC type, composite resin, and adhesive strategy. This study evaluated the shear bond strength (SBS) of monochromatic and nanohybrid composite resins bonded to resin-modified (RMGIC) and self-cure GIC using etch-and-rinse and self-etch adhesive protocols. Eighty standardized GIC specimens (4 ×&

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

Large language models (LLMs) are explored as clinical decision-support tools in complex medical fields. However, their reliability and clinical usefulness in multidisciplinary management of pituitary adenomas remain insufficiently evaluated using validated, clinician-based frameworks. Do LLMs differ in informational quality, clinical reasoning, and expert satisfaction when applied to pituitary adenoma-related clinical scenarios? A prospective comparative study evaluated three LLMs: ChatGPT-5.0, Claude Opus 4.1, and Gemini 2.5 Flash. A standardized prompt set covering general knowledge, surgical decision-making, endocrine evaluation, patient education, and MRI-based scenarios was submitted to each model identically. Outputs were anonymized and independently assessed by 10 board-certified doctors using three validated instruments: the Quality Assessment of Medical Artificial Intelligence (QAMAI), the Artificial Intelligence Performance Instrument (AIPI), and the Artificial Intelligence Satisfaction and Performance Evaluation Questionnaire (AISPE-Q). Claude Opus 4.1 achieved the highest performance across all major domains. Aggregate QAMAI scores were highest for Claude Opus 4.1 (4.39 ± 0.66), compared with ChatGPT-5.0 (4.12 ± 0.74) and Gemini 2.5 Flash (4.07 ± 0.76; p = 0.018). Clinical reasoning assessed by AIPI was superior for Claude Opus 4.1 versus Gemini 2.5 Flash and ChatGPT-5.0. Strong correlations were observed between informational quality, reasoning performance, and satisfaction. LLMs exhibit significant variability in performance when managing pituitary adenomas. Claude Opus 4.1 demonstrated the highest levels of informational quality, reasoning depth, and expert trust. While LLMs may serve as supportive adjuncts in multidisciplinary pituitary care, structured evaluation and expert oversight remain essential before clinical integration. 2 - Prospective comparative diagnostic accuracy study. To evaluate and compare the performance of nine contemporary LLM configurations on sleep medicine certification examination-aligned questions, analyzing version differences, pricing tiers, and subdomain competencies. Cross-sectional comparative analysis of 197 multiple-choice questions structured according to American Academy of Sleep Medicine (AASM) certification standards. Nine LLM configurations were evaluated: ChatGPT (GPT-3.5 free, GPT-4o paid), Gemini (2.5 Flash free, 2.5 Pro paid), Claude (3.7 Sonnet previous, Opus 4 paid), Deepseek V3 (free), xAI Grok3 (free), and Llama 3 (free). Each question was posed three times in independent sessions to minimize response variance. The first complete response from each iteration was recorded, and final accuracy was determined using strict 3/3 concordance criterion (correct only when all three iterations yielded identical correct answers). While alternative scoring approaches exist (single-try accuracy, 2/3 majority voting), the strict concordance method was selected as primary metric to minimize stochastic variation and ensure robust performance estimates. Supplementary analyses using majority voting (2/3) yielded consistent model rankings with marginally higher absolute accuracy values. Performance metrics included overall accuracy rates, 95% confidence intervals, and subdomain-specific analyses across seven sleep medicine categories. Statistical analyses employed Pearson's chi-square test for heterogeneity and McNemar's test for pairwise comparisons. This text-based simulation evaluated model performance on certification-style questions, though it does not replicate actual clinical examination conditions. Model performance demonstrated significant heterogeneity (χ 2 = 101.95, df = 8, p < 0.001), with accuracy rates ranging from 68.5% to 95.9%. Gemini 2.5 Pro achieved the highest overall accuracy (95.9%, 95% CI: 93.2-98.7%), followed by Claude Opus 4 (93.9%, 95% CI: 90.6-97.2%) and ChatGPT GPT-4o (93.4%, 95% CI: 89.9-96.9%). Premium versions consistently demonstrated superior performance compared to free alternatives, with performance differences ranging from 5.1 to 8.6 points (all p < 0.05). Subdomain analysis revealed the highest performance consistency in Secondary Sleep Disorders (92.0% mean accuracy) and the greatest variability in Diagnostic Methods (85.9% mean accuracy). Sensitivity analysis comparing three scoring criteria (single-try ≥1/3, majority voting ≥2/3, strict concordance 3/3) revealed that scoring methodology had minimal impact on model rankings (Spearman's ρ = 0.879-1.000, all p < 0.01). Majority voting and strict concordance yielded identical accuracy rates in seven of nine models due to high response consistency (95.8% average). Eight of nine models exceeded the 80% reference benchmark under all three scoring criteria. Contemporary LLMs demonstrate substantially improved performance compared to previous evaluations, with premium models exceeding the 80% reference benchmark. However, these results reflect performance on a certification-aligned question bank rather than the official board examination itself. The significant performance advantage of paid versions raises important considerations regarding equitable access to AI-enhanced medical education and clinical decision support tools. As artificial intelligence (AI) models evolve into their next generations, their application in specialized medical fields requires rigorous validation. While large language models (LLMs) have shown promise in general medicine, their reliability in complex gynecological clinical reasoning remains under-explored. This pilot study aimed to comparatively assess the knowledge retention, safety, and reasoning limitations of advanced AI chatbots in gynecology using a constrained zero-shot multiple-choice question (MCQ) format. A total of 70 text-based MCQs covering seven core gynecological modules were adapted from "USMLE Step 1 Sample Test Questions". The questions were administered to four advanced AI models: ChatGPT-5, Gemini-3, DeepSeek-V3.2, and Claude-4.5-Opus. To simulate a rapid-retrieval clinical scenario, models were tested under "zero-shot" conditions with a constrained prompt prohibiting reasoning steps. We performed both quantitative statistical analysis (Kruskal-Wallis, Cochran's Q) and qualitative error analysis to identify specific failure modes. Contrary to expectations for advanced models, overall accuracy was unsatisfactory: Gemini-3 (32.86%), DeepSeek-V3.2 (30.00%), ChatGPT-5 (25.71%), and Claude-4.5-Opus (21.43%). Significant performance disparities were observed across modules. Notably, ChatGPT-5 scored 0.00% in Infertility, while DeepSeek-V3.2 reached 70.00% in Common Benign Conditions. Qualitative analysis revealed three critical failure patterns: (1) semantic association bias (confusing high-probability diseases with symptom-specific diagnoses), (2) spatial anatomy confusion, and (3) genetic logic reversal. No significant correlation was found between item difficulty and accuracy (p > 0.05). Under constrained non-reasoning prompts, even next-generation AI chatbots demonstrate unsatisfactory performance in gynecology. The qualitative analysis suggests that models often rely on probabilistic keyword matching rather than physiological simulation, leading to theoretically dangerous clinical errors (e.g., misdiagnosing adrenal enzymes). While potential exists, current reliability is insufficient for unsupervised use in gynecological education. These findings highlight the critical need for "chain-of-thought" prompting and human expert oversight. Rehabilitation medicine faces a significant challenge due to the rising demand for services coupled with a shortage of specialized professionals. Large Language Models (LLMs) show promise for enhancing clinical efficiency, but their evaluation has been

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

The number of patients receiving immune checkpoint inhibitor (ICI) therapy for cancer is expected to increase further; hence, heightened awareness of immune-related adverse effects (irAEs) such as hypophysitis (ICI-Hp) is essential. Acute ICI-Hp is a common endocrine irAE of ICI therapy, and our aim was to describe its diagnostic pattern, treatment outcomes, endocrinopathies, and recovery. Records and imaging of all patients with ICI-Hp (n = 22), referred to a dedicated endocrine-ICI clinic, were retrospectively reviewed. The median time for onset of ICI-Hp was 13 weeks (IQR 9, 17), after the 3rd (IQR 3, 4) cycle of therapy. 55% of patients were female, with a median age of 67 years (IQR 53, 74), and 77% had metastatic melanoma. A combination of ipilimumab and nivolumab was used in 68% of those developing ICI-Hp. Headache (64%), fatigue (77%), nausea (64%), and hyponatraemia (41%) were the most common symptoms at presentation. Secondary adrenal insufficiency (SAI) was seen in 100%, secondary hypothyroidism (SH) in 41%, and secondary hypogonadism (SHG) in 27%. An enlarged pituitary gland (64%), thickened stalk (50%), mild optic chiasm compression (n = 3), and asymptomatic pituitary enlargement (n = 1) were noted on pituitary imaging. Glucocorticoid (GC) treatment regimens included intravenous methylprednisolone (IV MPP) (n = 4), prednisolone (n = 8), dexamethasone (n = 1), and oral hydrocortisone stress dosing for 48 h (n = 6). Complete resolution of symptoms and significant resolution of imaging findings were noted in all, independent of regimen. Acute psychosis was noted with IV MPP (n = 1). None recovered SAI during follow-up, whilst recovery of SH and SHG was noted in 33% and 67%, respectively. Additionally, new-onset type 1 diabetes developed in 18%, with DKA in 3 patients. ICI-Hp is common and potentially associated with serious complications in the absence of prompt recognition and treatment. Assessment of recovery of the HP-thyroid and HP-gonadal axes is important; however, ACTH deficiency is more likely to be permanent, hence requiring long-term GC replacement and appropriate patient education. Occurrence of ICI-Hp is most commonly seen after the 3rd cycle of combination ICI therapy, and in the future it may be appropriate to warn treating physicians (and perhaps patients) of the symptoms to flag after the third cycle of combination immunotherapy. Magnetic resonance imaging using hyperpolarized (HP) [1-13C]-pyruvate enables assessment of pyruvate metabolism in vivo and offers new insight into metabolic changes in response to cancer therapy. Widely used semi-quantitative metrics of pyruvate metabolism can be affected by physiological factors that are extrinsic to intracellular metabolism. A validated pharmacokinetic (PK) model for analysis of intracellular pyruvate metabolism is needed to enhance the accuracy of quantitative metrics and clinical translation of metabolic MRI using HP pyruvate. A PK model with two physical compartments and two chemical pools was developed to analyze the conversion of labeled pyruvate into lactate in vitro. Cells exposed to [U-13C3]-pyruvate were analyzed using pseudo-dynamic ion-coupled mass spectrometry (IC-MS) while cells exposed to HP [1-13C]-pyruvate were analyzed using dynamic NMR. The model was extended to incorporate a third physical compartment for vascular delivery, and quantification of changes in pyruvate metabolism in a patient with ATC was compared against semi-quantitative metrics. Good correspondence between complementary quantitative measures of pyruvate metabolism using IC-MS and NMR support the use of this framework as a foundation for quantitative analysis of HP pyruvate metabolism in vitro and in vivo. The three-compartment model identified changes in vascular delivery separately from changes in intracellular pyruvate metabolism, revealed greater heterogeneity in metabolic activity, and identified areas of persistent high metabolic activity against an overall reduction in tumor metabolism after 8 days of treatment. This framework for analysis provides a validated approach and demonstrates feasibility for quantitative evaluation of HP pyruvate metabolism in vivo. Non-variceal upper gastrointestinal bleeding (NVGIB) represents an urgent medical condition with high mortality. Standard endoscopic therapies (ST) still carry a high rebleeding rate. Novel modalities such as the over-the-scope clip (OTSC) and hemostatic powder (HP) could be promising alternatives, but their efficacy and cost-effectiveness remain to be explored. A network meta-analysis and cost-effectiveness analyses were conducted to compare OTSC vs. HP vs. ST. Primary endpoints include 30-day rebleeding and 30-day further bleeding. Markov models with a 12-month time horizon were created across 3 different healthcare settings: the United States (US), Thailand with Boston Scientific products (TH-BOS), and Thailand with China-manufactured alternatives (TH-CHN). Incremental cost-effectiveness ratio (ICER) was evaluated at a willingness-to-pay (WTP) of $100,000 per quality-adjusted life year (QALY) for the US model and THB150,000 per QALY for the TH-BOS and TH-CHN models. Ten RCTs with 1,120 NVGIB patients were included in the NMA. Lowest 30-day rebleeding was seen in OTSC (P-score:0.996), followed by ST (0.296) and HP (0.208). Similarly, OTSC also achieved lowest 30-day further bleeding (0.906), followed by HP (0.570) and ST (0.024). In CEA, the US model reported OTSC as a dominant approach compared to HP (ICER: -$314) and ST (-$3,112). In the TH model, OTSC still dominated ST (ICER:-THB28,423 for TH-BOS and -22,858 for TH-CHN) and was more cost-effective than HP (THB1,833 for TH-BOS and THB2,026 for TH-CHN). OTSC was superior to HP and ST in terms of efficacy and cost-effectiveness, favoring its use as a first-line endoscopic hemostasis intervention for NVGIB. To quantitatively assess left ventricular (LV) myocardial work (MW) in pregnant women with autoimmune diseases (AD) using left ventricular pressure-strain loop (PSL) and explore its clinical implications. Ninety-six participants were enrolled between September 2020 and September 2022 at the Affiliated Hospital of Inner Mongolia Medical University, including 33 pregnant women with AD (AD-P group), 26 non-pregnant AD patients (AD group), and 37 healthy pregnant women (H-P group). Clinical data, conventional echocardiography, two-dimensional speckle-tracking, and LV-MW analyses were obtained. Group comparisons and correlations between baseline characteristics and MW parameters were analyzed. Analysis of covariance (ANCOVA) and partial correlation were used for adjusted comparisons and associations. Following adjustment, the AD-P group demonstrated increased LV volume and lower apical constructive work (CW) compared to the AD group, while global MW indices were similar. Compared with H-P group, AD-P patients had lower E/A, increased LV volumes, E/e', and peak strain dispersion (PSD). After adjustment, AD-P had reduced global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and apical-CW, while PSD remained higher. LV myocardial work detected subclinical LV dysfunction in pregnant women with autoimmune disease. Apical-CW showed a consistent reduction in AD-P. These findings suggest that myocardial work, especially apical CW, provides incremental value over global longitudinal strain (GLS) in autoimmune pregnancies. This report describes the case of a 77-year-old man undergoing chemotherapy for synchronous lung cancer and rectal cancer. After receiving tegafur-uracil (UFT) plus leucovorin in combination with bevacizumab for rectal cancer, he developed exertional dyspnea. Chest computed tomography revealed diffuse bilateral centrilobular nodules and ground-glass opacities, suggesting a hypersensitivity pneumonia (HP) pattern of dr

Optoelectronic advances have boosted interest in noninvasive rosacea treatments. Among them, pulsed dye laser (PDL), intense pulsed light (IPL), and radiofrequency (RF) therapy have been used to treat erythematotelangiectatic rosacea (ETR), and some therapeutic effects have been reported, but comparative studies are lacking. This study aimed to compare the efficacy and safety of PDL, IPL, and RF therapy for the treatment of ETR. A retrospective evaluation was conducted of patients with ETR who completed phototherapy between June 2019 and June 2024. The treatment protocol included two sessions of 585 nm PDL therapy (6-week interval), three sessions of IPL (M22 590 filter) therapy (590-1200 nm, 4-week interval), or six sessions of multisource 3DEEP RF therapy (2-week interval), with a follow-up visit at 12 weeks post-final treatment. The clinical efficacy evaluation consisted of the Clinician Erythema Assessment (CEA) scale, patient self-assessment (PSA) scale, the overall efficacy rate, and the Rosacea-Specific Quality of Life instrument (RosaQoL). Safety was evaluated in terms of adverse reactions such as pain, purpura, erythematous edema, blistering, hyperpigmentation, and scarring. This study included 120 patients with ETR treated with PDL, M22 590, or RF therapy. Intragroup analysis revealed significant decreases in the CEA scale, PSA scale, and RosaQoL scores after treatment (p<0.001). The efficacy rates were 57.50%, 45.00%, and 67.50% for PDL, M22 590, and RF therapy, respectively, and no statistically significant intergroup differences were observed. Safety analysis confirmed that all the treatments were well tolerated. PDL, IPL and RF therapy all produced short-term improvements in erythema and quality of life in patients with ETR. RF showed comparable efficacy with better tolerability, suggesting a comfortable, low downtime option, while PDL and IPL are vascular-targeted tools. These exploratory findings require confirmation in longer, dose-standardized prospective studies. The adenovirus E3 region's immune-modulating genes (gp19K, Adenovirus Death Protein [ADP], E3B) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (GM-CSF). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (delgp19K), M20 (delgp19K and ADP), M22-0 (delgp19K and E3B), and their GM-CSF-armed derivatives, systematically evaluating the impact of ADP and E3B deletions on viral replication, tumor cell lysis, immune modulation, and in vivo antitumor activity. Key findings revealed that gp19K/ADP deletion OAd prolonged intracellular viral replication, creating a "viral bomb" effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression. Gp19K/E3B deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models, gp19K/ADP deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated gp19K/ADP deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control (L. casei-pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders. The Mueller matrix has the capability of providing the complete polarisation information about the response of a medium to the incident polarised light. In this work, we report that the anisotropic structures of non-stained melanoma slices can be identified directly through the Mueller elements. It is observed that the elements M12, M22 and M24 show a high degree of similarity with the three polarisation parameters (the x-y linear diattenuation, the x-y linear depolarization and the ±45° linear birefringence), with PSNR values of 33.4 dB, 35.7 dB and 40.0 dB, respectively. From images of M12, M22 and M24, the cell nuclei and intercellular stroma in the melanoma dermis can be identified with higher contrast. The values of these elements are specific: for the cell nuclei, M22 ranges from -0.75 to -0.27 and M12 ranges from -0.12 to -0.04; for the extracellular matrix, M22, M12 and M24 fall within -0.16 and -0.07, 0.06 and 0.16 and 0.09 and 0.57, respectively. Finally, a theoretical analysis is presented to explain the observations. The results obtained in this is helpful for clinic applications of Mueller matrix images where a method of interpreting measured Mueller matrices rapidly and accurately is essential. Acinetobacter baumannii is a bacterial pathogen frequently implicated in healthcare-associated infections, with limited effective treatment options due to widespread antibiotic resistance. Sulbactam/durlobactam is a novel β-lactam/β-lactamase inhibitor (βL/βLI) combination recently approved for the treatment of hospital-associated bacterial pneumonia and ventilator-associated bacterial pneumonia due to A. baumannii. We evaluated the in vitro activity of sulbactam/durlobactam alone and in combination with 15 clinically relevant antibiotics against 22 A. baumannii clinical isolates, including 21 extensively or pandrug-resistant strains (M1-M22) and one metallo-β-lactamase (MBL)-producing strain (BAA-3302). Susceptibility testing, chequerboard synergy assays, and static time-kill assays were performed to assess antimicrobial interactions. All 21 XDR/PDR isolates were susceptible to sulbactam/durlobactam (MIC < 4/4 mg/L), while the MBL-harbouring strain BAA-3302 showed intermediate susceptibility (MIC = 8/4 mg/L). Chequerboard assays revealed consistent synergy between sulbactam/durlobactam and multiple β-lactams and βL/βLI agents, including cefepime, meropenem, cefiderocol, ceftazidime-avibactam, and piperacillin-tazobactam, with ≥95% of strains showing synergistic effects. Selected combinations demonstrated rapid and sustained bactericidal activity against select strains in time-kill assays. Combinations

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Driving supports independence and quality of life in later life but is vulnerable to age-related and/or disease-related decline. While cognitive impairment is a well-recognized risk for unsafe mobility, the contribution of sensorimotor function is less understood. We studied 374 cognitively normal older adults (Clinical Dementia Rating = 0 at baseline) enrolled in the DRIVES Project. A SensoryMotor Impairment Index (SMI) was constructed from six domains (grip strength, gait speed, reaction time, hearing, vision, olfaction) and categorized as 0, 1, 2, or ≥ 3 impairments. Naturalistic driving was continuously monitored using in-vehicle GPS dataloggers between 2019 and 2025. Linear mixed-effects models tested whether longitudinal driving trajectories differed by baseline SMI, adjusting for age, sex, race, education, body mass index, and cognition (Preclinical Alzheimer's Cognitive Composite). At baseline, participants with higher SMI burden were older and had lower cognitive scores (both p < 0.01). Over time, greater sensorymotor impairment was associated with faster declines in driving exposure and spatial range. Compared with SMI = 0, participants with SMI ≥ 3 showed steeper reductions in nighttime trips (-0.050 vs. -0.037 trips/month), long-distance trips (> 20 miles; p < 0.001), and maximum trip distance (p = 0.009), and greater contraction of driving space (entropy and radius of gyration; p < 0.001). Self-reported driving behaviors showed that participants with higher SMI drove fewer days per-week and were more likely to avoid night driving (p < 0.01). Rates of self-reported adverse driving events (e.g., crashes or citations) did not differ significantly across SMI groups, consistent with compensatory self-regulatory behaviors. Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving. Mid-fibular stress fractures are rare in the pediatric population and frequently present a diagnostic dilemma due to their subtle clinical presentation. In young, active children, the localized pain and associated periosteal reaction can closely mimic aggressive pathologies, such as primary bone malignancies or osteomyelitis, often leading to unnecessary parental anxiety and invasive diagnostic procedures. We report the case of a 4-year-old boy presenting with a 2-week history of an antalgic gait and localized tenderness over the left fibular shaft in the absence of acute trauma. While initial plain radiography revealed a reactive cortical lesion suspicious for malignancy, subsequent cross-sectional imaging with computed tomography and magnetic resonance imaging identified a subtle fracture line and circumferential periosteal thickening, confirming a mid-fibular stress fracture. The patient was managed conservatively with restricted weight-bearing and analgesics, with complete clinical recovery and radiographic bone remodeling documented at 2-month follow-up. This case underscores the necessity of maintaining a high index of suspicion for stress-related injuries in the pediatric population, even in the absence of a high-impact mechanism. A comprehensive diagnostic approach utilizing multimodal imaging is essential to differentiate benign stress fractures from more ominous conditions, ensuring appropriate conservative management and avoiding the risks associated with unnecessary biopsy or over-treatment. Tyrosine kinase inhibitors (TKIs) are widely used in cancer therapy and are known to induce hypothyroidism in some patients, though the mechanisms remain unclear. We describe a 58-year-old man with metastatic gastrointestinal stromal tumor who developed clinical hypothyroidism during TKI treatment. Imaging revealed thyroid enlargement, and fine-needle aspiration yielded indeterminate cytology. The patient subsequently underwent thyroid lobectomy, which revealed a unique pattern of thyroiditis with multiple hyaline nodules containing entrapped follicular cells and scattered immune cell infiltration. Postoperatively, the patient was in a good clinical condition, but persistently elevated thyroid-stimulating hormone concentrations despite normal T4 concentrations were likely due to pre-existing TKI-induced thyroid dysfunction limiting compensatory function after hemithyroidectomy. The above-mentioned histological presentation is atypical for conventional thyroiditis and may represent a distinct pathological response associated with TKI therapy. The clinical, cytological, and histological findings in this case suggest a potential link between TKIs and thyroid dysfunction, highlighting the need for increased awareness of thyroid complications during targeted therapy. This case underscores the importance of considering iatrogenic causes in new-onset hypothyroidism in oncology patients and suggests that distinct histological features may serve as clues to the underlying pathogenesis. Cutaneous infections contribute to an important cause of all dermatological lesions. Most of the superficial cutaneous infections are diagnosed based on clinical findings and with adjunct diagnostic modalities like potassium hydroxide mounts, tzanck smears, Gram stain, and other microbiological investigations and are treated without the necessity of histopathological examinations. Histopathology is indispensable in some instances, especially when the above-mentioned investigations are non-contributory for diagnosis, and in situations where there is a doubt that the organisms isolated in culture represents contamination and in deep cutaneous infections to define tissue and vascular invasion. Hence, this study aimed at studying the spectrum of non-lepromatous cutaneous infections that required histopathological examination for diagnosis. This is a record-based retrospective study conducted in the Department of Pathology for 4 years. All diagnosed cases of cutaneous infections that required histopathological examinations for diagnosis were included in the study. Leprosy cases were excluded from the study. Details were collected retrospectively from the records and were analysed manually. Results: There were totally 112 cases of cutaneous infections diagnosed on histopathology during the study period, of which 14% were bacterial, 15.2% were viral, 77% were fungal, and 3.6% were parasitic. Actinomycosis was the common bacterial infection, human papillomavirus-related lesions were the common viral infections, pheohyphomycosis was the common fungal infection, and cysticercosis was the common parasitic infection. Histopathological examinations play an important role in management of cutaneous infections as they not only aid in primary diagnosis but also give information on host reaction, severity of the infection, and the presence of tissue invasion, which are crucial information for undertaking treatment decisions. To investigate the effects of combined Levocarnitine and Alprostadil therapy on renal function, oxidant-antioxidant balance, and systemic inflammation in patients with end-stage diabetic nephropathy (ESDN). This retrospective study included 104 ESDN patients admitted to our hospital between April 2021 and April 2023 who met all inclusion criteria. All patients were on maintenance hemodialysis for chronic kidney failure due to ESDN. Based on the treatment regimen received, patients were divided into two groups: the control (n=51) received intravenous Alprostadil (20 μg/day) for 30 days in addition to standard care, and the observation group (n=53) received additional intravenous Levocarnitine (1.0 g/day) for 30 days. Clinical efficacy, renal function parameters [blood

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Genitourinary syndrome of menopause (GSM) is a chronic condition that impairs quality of life and sexual function. Fractional CO2 laser therapy is a non-hormonal option, but large real-world data on symptom trajectories, durability, and ultrasonographic vulvar changes are limited. We evaluated symptom trajectories, responder rates, exposure-outcome associations, and vulvar tissue changes in a clinical cohort. We conducted a retrospective observational study at a single clinic in Japan. From 2016 to 2023, 826 women underwent fractional CO₂ vaginal and vulvar laser therapy (2,129 sessions). Symptoms were assessed using VAS (0-10) scores for six domains. Short-term outcomes were evaluated 20-59 days after the first session (n = 327), and long-term outcomes 10-14 months after the final session (n = 94). Responders were defined as a ≥2-point VAS improvement among women with baseline VAS ≥2. outcomes included ultrasonographic labia majora thickness; post-treatment imaging corresponded to the same windows when paired measurements were available. Patient satisfaction and adverse events were recorded. Mean age at first treatment was 61.9 ± 10.2 years (range, 29-87). All six symptoms improved short term, with the largest improvements typically in dyspareunia and vaginal dryness. At 10-14 months, improvements in dryness and urinary leakage attenuated, whereas dyspareunia was most durable. Labia majora thickness increased overall (16.9 ± 4.5-18.9 ± 3.1 mm), with thickening in 81.5% of women with paired measurements. Higher responder rates were observed among women receiving more sessions; however, these findings are associational and may reflect baseline severity and follow-up engagement. Satisfaction was high, and no serious adverse events were observed. In this real-world cohort, fractional CO2 vaginal and vulvar laser therapy for GSM was associated with reduced symptom severity and ultrasonographic thickening of the labia majora in a subset with paired measurements. Given the retrospective uncontrolled design, incomplete follow-up, and placebo effects in sham-controlled trials, findings should be interpreted as descriptive associations, not causal effects. Controlled studies are needed to confirm effectiveness, durability, and maintenance strategies. Energy-based devices (EBDs), including vaginal laser and radiofrequency therapies, have been proposed as minimally invasive treatments for stress urinary incontinence (SUI), but evidence remains limited and inconsistent. We hypothesised that EBDs would provide greater symptom improvement than sham, particularly in women with mild to moderate SUI. Following PRISMA guidelines, we searched Medline, Embase, the Cochrane Library, and One Search for randomised controlled trials (RCTs) comparing EBDs with sham in women with SUI, with at least 1 month of follow-up. The primary outcome was change in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) scores. Two reviewers independently performed data extraction and RoB-2 assessment. Random-effects meta-analyses using restricted maximum likelihood estimation were conducted. Ten RCTs (11 datasets; ~ 850 women) were included. Using a random-effects model with Knapp-Hartung adjustment, the pooled EBD analysis showed a mean difference of -1.08 points (95% CI -2.08 to -0.08), indicating a statistically significant improvement with EBD. The prediction interval (-3.63 to 1.48) suggests a wide range of possible effects, including no benefit. Heterogeneity was moderate (I2 = 53%). Subgroup analysis of non-ablative Er:YAG laser showed the strongest and most homogeneous effect (MD -1.42; 95% CI -2.55 to -0.28; I2 = 29%). CO2 laser findings were inconsistent, and evidence for radiofrequency was insufficient. Adverse events were mild and transient. EBDs may improve SUI symptoms compared with sham, with the most consistent benefit observed for non-ablative Er:YAG laser. However, effects are modest and short-term. High-quality RCTs with standardised protocols and long-term follow-up are needed. Skin graft scars frequently remain hypertrophic, stiff, tethered, and dyschromic despite standard care. These scars are characterized by chronic inflammation, biomechanical rigidity, and surface irregularity, and often respond poorly to conventional fractional resurfacing or intralesional triamcinolone monotherapy due to limited penetration in thick, mature grafted tissue. Pinholxell Therapy is a standardized dual-step CO₂ laser protocol that combines deep macro-pinhole column creation (∼1 mm) with an immediate fractional CO₂ overlay, aiming to achieve simultaneous deep dermal release and surface normalization within a single session. We retrospectively analyzed 117 consecutive patients with mature graft-site scars treated with repeated sessions of the standardized dual-step Pinholxell CO₂ laser protocol at approximately 2-month intervals. Most patients underwent multiple treatments over an extended remodeling period. Scar outcomes were evaluated before and after treatment using the Vancouver Scar Scale (VSS) and the Observer Scar Assessment Scale (OSAS). Marked improvements were noted across all scar domains. The total VSS score decreased from 7.76 ± 2.22 to 1.47 ± 1.09 (p < 0.001; 81.1% reduction), with the greatest improvements in pigmentation and vascularity. The OSAS six-item total score improved from 31.78 ± 7.09 to 11.44 ± 2.59 (p < 0.001), and the overall opinion score improved from 7.15 ± 1.41 to 2.38 ± 0.48 (p < 0.001). The dual-step macro-pinhole column plus fractional CO₂ protocol produced substantial and consistent improvement in mature graft-site scars, supporting Pinholxell Therapy as a reproducible, office-based option for functional and aesthetic scar rehabilitation. In this study, we conducted a randomized controlled clinical trial to investigate the effectiveness and safety of punch excision versus manual fractional technology (MFT) in patients undergoing intralesional triamcinolone acetonide and 5-fluorouracil injection. Patients with keloid were randomly divided into two groups: One received punch excision combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (punch excision + TAC&5-FU), and the other received MFT combined with intralesional triamcinolone acetonide and 5-fluorouracil injection (MFT + TAC&5-FU). Designed treatments and regular evaluations were conducted. The significant improvement was observed in both groups. Regarding the effectiveness of different combined therapies, MFT combined with TAC&5-FU demonstrated a greater improvement of mVSS, POSAS, and DLQI without statistical differences when comparing with those of punch excision combined therapy. Likewise, the injection times and adverse events were generally similar across both groups. This study demonstrated that punch excision combined with TAC&5-FU, as well as MFT combined with TAC&5-FU, was promising therapeutic options for keloids without a notable difference in effectiveness and safety. A single-blinded randomized clinical trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Post-acne scarring is a prevalent dermatological concern with significant impact on quality of life. Fractional CO2 laser (FCL) and microneedling radiofrequency (MNRF) are widely used treatments, but their comparative efficacy and safety require further synthesis. This meta-analysis was conducted to compare the efficacy a

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

Breast ultrasound is widely used for cancer screening, but data scarcity and annotation challenges hinder deep learning adoption. Synthetic image generation offers a promising solution to enhance training datasets while preserving patient privacy. However, problems such as inadequate quality of synthesized images and the need for large amounts of data to train the synthesis models remain significant. We propose a three-stage latent diffusion model (LDM) workflow-enhanced by Vision Transformers and fine-tuned with low-rank adaptation-that synthesizes realistic malignant and benign breast ultrasound images directly from healthy samples while simultaneously generating accurate segmentation masks. Stage division significantly reduces the task complexity of a single synthesis model. Applied to the BUSI dataset (133 healthy, 487 benign, and 210 malignant images), the method generates synthetic cases of each tumor type. A ResNet101 classifier could not reliably distinguish synthetic from real images (AUC = 0.563), indicating high visual plausibility. Quantitative metrics confirmed strong fidelity: Fréchet inception distance = 15.2 and inception score = 1.79, indicating low distributional divergence in feature space and high similarity to real data. When used for training a U-Net segmentation model, the augmented dataset improved the F 1 -score from 0.870 to 0.896, demonstrating substantial gains in diagnostic accuracy. These results show that the proposed three-stage LDM can generate high-quality, anatomically coherent breast cancer images from healthy controls, effectively alleviating data scarcity and enabling more robust training of medical AI systems without compromising clinical realism. Delayed wound healing in diabetes mellitus (DM) is closely associated with endothelial mitochondrial dysfunction and impaired mitophagy. We therefore developed a liquid dermal matrix (LDM) and investigated its therapeutic efficacy and underlying mechanisms in diabetic wound repair. The release behavior and biocompatibility of LDM were characterized. Its therapeutic effects were evaluated in a streptozotocin (STZ)-induced diabetic mouse full-thickness wound model, and mechanistic studies were conducted in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). LDM exhibited sustained protein release over 96 h. In STZ-diabetic mice, topical application of Gel + LDM markedly accelerated wound closure; the wound closure rate at day 12 increased from 68.87 ± 3.98% in the Gel group to 94.80 ± 1.35% in the Gel + LDM group (P < 0.001). Laser speckle imaging confirmed enhanced wound perfusion at day 12, with perfusion units increasing from 489.96 ± 33.74 (Gel) to 707.21 ± 24.21 (Gel + LDM) (P < 0.001). Histological analyses revealed improved re-epithelialization and collagen remodeling, alongside increased angiogenesis as indicated by elevated CD31 and VEGFA staining. Mechanistically, in HG-treated HUVECs, LDM restored autophagic flux, evidenced by increased LC3-II and reduced P62 accumulation, and promoted PINK1/Parkin-dependent mitophagy. This was accompanied by attenuated mitochondrial fragmentation, reduced mtROS, and improved mitochondrial membrane potential (ΔΨm). Functionally, LDM improved endothelial proliferation, migration, and tube formation, while these protective effects were largely attenuated by 3-MA, MG-149, or PINK1 knockdown, supporting a mitophagy-dependent mechanism. LDM accelerates diabetic wound healing and improves wound perfusion by restoring mitophagy and mitochondrial homeostasis in endothelial cells, highlighting LDM as a promising therapeutic strategy for DM-associated chronic wounds. Yttrium-90 resin microspheres selective internal radiation therapy ( 90 $$ {}^{90} $$ Y-SIRT) has been increasingly adopted worldwide as a locoregional treatment option for appropriately selected patients with liver malignancies. The key to ensuring that the tumor receives an adequate radiation dose while minimizing the dose to normal tissues is to optimize the trade-off between tumor control and the probability of normal tissue complications. To accurately determine a patient's internal radiation dose, pre-treatment dose planning and post-treatment dose verification using dosimetric methods are recommended and increasingly considered best practice in 90 $$ {}^{90} $$ Y-SIRT, where feasible. Due to the increased demand for personalized treatment and dose accuracy in clinical practice, 90 $$ {}^{90} $$ Y-SIRT dosimetry has transitioned from organ-level to voxel-level dosimetry. This paper introduces the relevant principles and development history of 90 $$ {}^{90} $$ Y-SIRT dosimetry for resin microspheres. It also discusses the clinical performance, influencing factors and practical applications of relevant dosimetry methods. These include body surface area (BSA) method, MIRD multi-compartment model method, and partition model method; voxel-S-value (VSV); local deposition method (LDM); and Monte Carlo (MC) method. Finally, it covers the subsequent development of resin microsphere 90 $$ {}^{90} $$ Y-SIRT dosimetry. We address computed tomography (CT) metal artifacts reduction (MAR) using a generative deep-learning model in the imaging physics framework. Existing deep learning-based MAR methods, though promising, generally lack explicit physical modeling of artifact formation and rely heavily on data-driven mappings. The absence of physics priors not only limits scalability, as they often require paired or task-specific datasets, but also makes such methods prone to hallucination, anatomical distortion, and unstable artifact suppression. We propose a novel self-supervised framework for CT MAR, integrating a lightweight multi-layer perceptron (MLP)-based beam-hardening correction with a conditional latent diffusion model (LDM). By incorporating a physics-informed correction step and an artifact-reproducing simulation technique, the framework aims to enhance scalability across diverse scenarios, reduce hallucination effects, and improve structural fidelity in the reconstructed images. The proposed MLP performs physics-driven polynomial correction, serving as a simplified but efficient alternative to existing approaches. Also, the proposed MLP implicitly incorporates sinogram consistency into its optimization objective, allowing case-specific adaptation and convergence toward the desired solution. Additionally, the learned MLP parameters are reused to simulate artifact-contaminated images from artifact-free scans, generating pseudo paired data for self-supervised training without requiring real paired datasets. A conditional LDM is trained on these synthetic pairs to remove residual artifacts. By operating in a low-dimensional latent space, the LDM significantly reduces inference time while maintaining high-quality reconstructions. The proposed method is evaluated on both the SynDeepLesion dataset and real clinical data, demonstrating superior artifact removal and structural preservation compared to the existing state-of-the-art MAR techniques. We particularly highlight the robustness, generalizability, and clinical applicability of the proposed framework. We proposed a self-supervised metal artifact reduction framework that combines MLP-based beam-hardening correction with a conditional latent diffusion model in the imaging physics framework. The MLP module provides physics motivated beam-hardening corrected CT images, while the residual artifact simulation strategy enables fully self-supervised training without the need for paired data. The proposed method demonstrated superior artifact suppression and structural preservation on both synthetic and clinical datasets, outperforming existing approaches. Injury to articular cartilage remains a major clinical challenge owing to its limited se

The manual identification of dental implant systems on radiographs is time-consuming, operator-dependent, and prone to diagnostic inaccuracies, particularly for patients where clinical documentation is lacking. The increasing variety of implant designs further complicates identification in prosthetic and surgical practice. The purpose of this study was to develop and evaluate a deep learning-based model for the automated identification of 7 implant systems (Adin, Dentium, Dionavi, Make It Simple (MIS), Nobel, Noris, and Osstem) using panoramic radiographs and periapical radiographs in an effort to enhance diagnostic efficiency and support clinical decision-making in prosthodontic care. A total of 4677 anonymized radiographic images with 8189 implants were curated and annotated using Roboflow with bounding boxes outlining fixture components. The preprocessing involved normalization, resizing to 640×640 pixels, and geometric augmentation (rotation, cropping, and blurring) to handle class imbalances. You Only Look Once (YOLO) v10 architecture, implemented with PyTorch, using CSPDarknet and PANet for multiscale feature fusion, was used to optimize real-time detection. Transfer learning used pretrained weights, with training for over 500 epochs (batch size: 32) on NVIDIA T4 GPUs. Data partitioning involved an 80:10:10 ratio (training: validation: testing), with performance evaluated using precision, recall, F1-score, and mean average precision (mAP). The model achieved a mAP of 98.3%, with mean precision, recall, and F1-score values of 93%, 86%, and 89%, respectively. Osstem implants demonstrated maximum discriminability (99% precision, 95% recall). In contrast, Nobel implants exhibited low recall (72.7%), attributed to the sparsity of the dataset (564 samples for Nobel compared with 2320 for Osstem) and similar radiopacity patterns. The YOLOv10 model demonstrated good performance in identifying dental implants, showing clinical promise for minimizing prosthetic mismatches. Subject to ethics and regulatory approvals, additional improvements involving 3-dimensional imaging and heterogeneous datasets may add precision and validate artificial intelligence as an evidence-based advance in implant dentistry. Implant identification is a pressing concern in dental implantology, and artificial intelligence (AI) has been evaluated for this purpose. YOLO, a state-of-the-art object detection model, is suitable for medical imaging; therefore, this study assessed YOLOv11-the latest iteration-for identifying 10 implant types in Indian clinical settings and compared its accuracy to that of dental professionals. A dataset of 3,161 radiographs, comprising both periapical and panoramic images of 10 implant types, was annotated and used to train and test YOLOv11. Training was performed on Google Colab using an NVIDIA Tesla T4 GPU (16 GB VRAM). A random sample of 200 radiographs was selected from the test dataset and presented to 50 dental practitioners for implant identification. Their responses were analysed and compared, using the chi-square test for statistical significance. YOLOv11 achieved precision of 0.87, recall of 0.85, an F1-score of 0.86, and an mAP50 of 0.899. The model achieved excellent classification accuracy for Adin (95%), MIS (94%), Bego (92%), ITI (96%), and Bicon (97%). Moderate accuracy was noted for Noris (82%), Osstem (85%), AlphaBio (88%), Dentium (77%), and Bioline (75%). YOLOv11 demonstrated higher overall accuracy and consistency than dental professionals. Dentists' accuracy ranged from 27% to 49%, whereas that of YOLOv11 ranged from 92% to 100%. YOLOv11 recognised most implant classes with over 90% accuracy, surpassing traditional manual techniques in implant detection. Although the model is dependable and efficient, certain aspects require improvement. The study also emphasises the significance of a region-specific approach for clinical relevance. The aim of our studdy is clinical evaluation of Platform switch hybrid zygoma implants. 117 zygomatic implants were followed up during this time. They included 55 Brånemark System zygoma implants, 38 Noris implants, and 24 novel iRES hybrid implants with platform switch. Bone quality and quantity are the prerequisite for successful implant treatment. Zygomatic implants are intended for patients with severely resorbed maxilla that cannot accommodate conventional implants without prior extensive bone grafting. Such regenerative procedures, like sinus lifts, prolong implant rehabilitation to several months (12-18). Furthermore, extensive grafts are less predictable showing varying degrees of graft resorption. Zygoma implants enable full, often immediate, reconstruction of the upper dental arch without the need for sinus lift treatment. The original zygoma protocol runs the implants through the sinus, requires general anesthesia, and positions the prosthetic platform of the implants on the palate, which makes prosthesis cumbersome. It also induces risk for post-op sinusitis. Extra-sinus approach with novel zygoma hybrid implants bypasses sinuses and positions the implant prosthetic platform on the crest allowing for same good prosthetics as on conventional dental implants. Furthermore, crestal threads and a platform-switch, of the novel zygoma design, increase implant anchorage and minimize marginal bone loss. The study presents evolution of zygoma implant rehabilitation protocol and zygoma implant design in our clinical practice over 15 years (2004-2019). Extra-sinus zygomatic implant placement lowers the risk of post-op sinusitis and makes procedure possible to be done in local anesthesia. The most common diagnosis for pediatric thrombocytopenia is immune thrombocytopenia. Nevertheless, in atypical cases, the hypothesis of an inherited thrombocytopenia has to be investigated. We report a series of cases of a newly described entity, genetic thrombocytopenia with mutation in the ankyrine 26 gene, diagnosed from the exploration of five pediatric cases of thrombocytopenia. This entity is characterized by a moderate thrombocytopenia with normal mean platelet volume, and poorly bleeding. Its transmission is autosomal dominant. Final diagnosis is made by sequencing of a short DNA region of ANKRD26 gene. This pathology can be considered as an hematological malignancy predisposition syndrome. We report the first cohort of pediatric patients diagnosed with thrombocytopenia with mutation in the ankyrine 26. The aim is to underline the specificities of this entity in children and bring it to the knowledge of pediatricians who may be in first place to manage these patients. • Genetic thrombocytopenia with mutation in the ankyrine 26 gene is a recently described entity, which seems to be considered as a predisposition for hematologic malignancies. • The first cohort has been reported in 2011, by Noris et al., in 78 Italian adult patients. What is New: • We describe clinical and biological features of the first pediatric cohort diagnosed with genetic thrombocytopenia with mutation in the ankyrine 26 gene. • It seemed important to consider the pediatric specificities of this entity to enable pediatricians to investigate, diagnose, and manage pediatric patients and their families. Noris and Remuzzi discuss a new study showing an association between atypical haemolytic uremic syndrome and a hybrid complement gene,CFH/CFHL1. Epidemics of tomato yellow leaf curl have occurred annually in greenhouse- and field-grown tomato (Lycopersicon esculentum Mill.) crops in southern Spain since 1992 (2). The nucleotide sequences of two tomato yellow leaf curl virus (TYLCV) isolates from this region, TYLCV-M (GenBank accession no. Z25751) and TYLCV-Alm (L27708), have been determined and these isolates are closely related to isolates reported from Italy (X61153 and Z28390), suggesting the existence of a geographical cluster of closely related TYLCV isolates in the Western Mediterranean Basin (2

The use of hyaluronic acid (HA) fillers is rising globally. Traditionally, the rheology of HA fillers has been subject to investigations for their use in facial soft tissues. Hitherto, there has been a significant gap in understanding their rheologic properties in body applications. The requirements for body fillers are different from facial fillers as they are applied for larger volume deficits, and experience greater mechanical stress. This study aims to fill this gap by analyzing the physicochemical and rheological properties of HA body fillers to guide clinical practice. Four commercially available HA-based body fillers were analyzed under standardized laboratory conditions. The physicochemical properties, including pH, osmolality, ion concentrations, clarity, and swelling factor, were assessed. Rheological properties, including storage modulus (G'), loss modulus (G″), complex modulus (G*), and tan delta (tan δ), were assessed between 0.1 and 1 Hz. The physicochemical analysis revealed no significant differences among the fillers, indicating uniform chemical stability. However, rheological analysis showed significant variations. Infini B Body exhibited the lowest G', G″, and G* values. In contrast, HYAcorp MLF1 and MLF2 displayed higher G' and G* values, indicating greater elasticity and stiffness. Consistent rankings between 0.1 and 1 Hz suggest stable mechanical performance under dynamic and sustained loading, supporting their suitability for high-load applications such as gluteal augmentation. Selecting HA body fillers based on their rheological properties is crucial for optimizing outcomes, particularly in body contouring procedures where mechanical demands differ from those of facial applications. Clinicians should tailor filler selection to the specific requirements of each body area. Further research is required to validate these findings in long-term clinical settings. This study sought to establish an experimental aneurysm model of visualizing coil insertion using radiolucent nylon coils. Moreover, this study aimed to clarify the characteristics and differences of each coil and use them clinically as indices of coil selection. The coil insertion test was performed on the 10 mm spherical silicone aneurysm model filled to a nylon coil volume embolization ratio of 11.8%. Five types of coil were randomly tested six times, and the distribution of the coils was analyzed by fluoroscopy imaging. Indices of "Area (mm2)," "Feret's diameter (mm)," and "Circularity" were calculated from the fluoroscopic images. Among the indices, only "Area" showed a significant difference between coils (p = 0.002). On multivariate analysis, "Area" of the ED Infini was larger than those of Target XL soft and Galaxy G3 (p = 0.018 and 0.026, respectively). Furthermore, the area of the 360 soft was larger than that of G3 (p = 0.049). Analysis of the correlation between these values and the coil configuration showed that "Area" was negatively correlated with the stock-wire diameter (r = -0.50; p = 0.004) and primary coil configuration (r = -0.65; p < 0.001). When inserting the coils in the early stage, although the difference between each coil is relatively difficult to obtain, knowledge on the proper use of the coils with differences in characteristics can help in selecting the coil most appropriate for the conditions. Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication. Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Develo

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Recurrent ERBB2-mutations have been recently documented in a small group of hybrid neurofibroma/schwannoma peripheral nerve sheath tumors (PNST) in patients with presumed sporadic schwannomatosis. Prompted by two cases of plexiform neurofibromas harboring Epidermal Growth Factor Receptor 2 (ERBB2) hot spot mutations, but lacking germline alterations, we sought to investigate the clinicopathologic features of PNST demonstrating this genetic alteration. ERBB2-mutant PNST cases were selected from the institutional molecular database, using a matched tumor-normal targeted DNA sequencing panel. Clinical history, radiologic findings and follow-up information were retrieved from chart review. Pathologic features, genomic and germline findings were reviewed. We identified 5 patients, all except one were females, with a median age of 34 years (range: 24-40). All revealed multiple PNSTs with a segmental distribution by imaging, including pelvis (n=2), upper limb (n=2), and stomach (n=1). None of the patients had family history or displayed clinical features of NF1, except for one patient with faded café-au-lait macules. All excised lesions were neurofibromas, including plexiform (n=4), intraneural with Schwann cell micronodules (n=2), and diffuse (n=1) subtypes. None of the cases showed features of schwannoma. All cases harbored ERBB2 kinase domain mutations (exon 19, n=3, exon 20, n=2, exon 21, n=1). One additional case had two concurrent ERBB2 mutations in exons 20 and 21. By germline testing, only one patient showed pathogenic variants (MUTYH mutation). None showed germline or somatic alterations in NF1, NF2, SMARCB1, LZTR1 or chromosome 22q loss. Patients had stable disease with no significant radiologic progression or malignant transformation; one being enrolled on a HER2-inhibitor trial for 7 years due to unresectable disease with satisfactory disease control. PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications. This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970's a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980's the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990's antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage. What is the relationship between constitutive CD138 expression in the endometrium and the reproductive tract microbiota composition? The presence of CD138+ cells in endometrial stroma is cycle-dependent and associated with impaired luteal phase endometrial timing but not altered vaginal or endometrial microbial composition. CD138-diagnosed chronic endometritis (CE) is associated with adverse reproductive outcomes including recurrent pregnancy loss (RPL) in uncontrolled studies. However, CD138 is constitutively expressed in the endometrium, potentially confounding the reported associations between CE, adverse endometrial function, and early pregnancy loss. Translational cohort study of a subset of 103 samples derived from 737 women embedded within the CERM trial, a double-blinded, randomized interventional trial evaluating the impact of pre-pregnancy antibiotic treatment for CE in RPL patients. Women aged ≥18 to <42 years, with a history of two or more first-trimester consecutive miscarriages were recruited from specialist RPL clinics. Endometrial biopsies, vaginal, ectocervical, and endometrial swabs were obtained 10 ± 4 days following a positive home ovulation test. Additional samples, including proliferative endometrium, were obtained from the Tommy's National Reproductive Health Biobank. Endometrial biopsies were processed for CD138 expression analysis and immunohistochemistry (IHC), histological dating based on Noyes' criteria, and molecular timing analysis. Metataxonomic profiling of microbiota was performed by sequencing of bacterial 16S ribosomal RNA genes alongside cytokine analysis. IHC revealed three patterns of CD138 immunoreactivity: predominantly membranous punctate staining, predominantly diffuse staining, and a mixed pattern. CD138 is constitutively expressed on the basolateral membrane of glandular epithelial cells and a subset of non-immune stromal cells. Stromal expression was very high (>200 CD138-positive stromal cells/10 mm2) in 26 out of 27 proliferative endometrial samples. While CD138 immunoreactivity in the stroma declines markedly following ovulation (Mann-Whitney U-test; P < 0.005), gene expression analysis demonstrated a reduction in SDC1 expression encoding CD138/syndecan-1, across the menstrual cycle. When compared to CD138-negative samples, conspicuous diffuse staining in the stromal compartment was associated with significantly earlier endometrial histological dating (P < 0.01) and lower molecular timing ratios (P < 0.01). Poor correlation between CD138 and immunoreactivity was demonstrated. Sequencing of paired vaginal and ectocervical swabs and endometrial Tao brush samples collected from 114 patients demonstrated tightly interconnected microbial composition throughout the reproductive tract. No significant difference in vaginal, ectocervical, or endometrial community state type with CD138 expression was demonstrated. Analysis of supernatants of vaginal and ectocervical swabs and Tao Brush revealed an inverse correlation between the severity of stromal CD138 immunoreactivity in endometrial stroma and secreted levels of IL-10, TNF-α, and VEGF (q < 0.05). Microbial and Metataxonomic raw data are available in the European Nucleotide Archive (Projects PRJEB83331 and PRJEB83332). This study relied on patient-reported ovulation-based timing. This was, however, associated with the provision of validated ovulation tests. In addition, the study is limited by lack of collection of data on the underlying fertility-related co-morbidities due to exclusion of known contributory co-morbidities at the point of recruitment. This study challenges the purported relationship between CD138+ CE and the pathophysiology of CE-associated RPL. The findings indicate endometrial CD138 levels are non-immune and non-bacterial driven and are associated with endometrial immaturity. CD138-based CE testing and treatment should not be performed outside of a research context. Funding was provided by the Efficacy and Mechanism Evaluation (EME) Programme a National Institute for Health and Care Research and Medical Research Council partnership (17/60/22). Further funding was from Tommy's National Centre for Miscarriage Research, and the Imperial National Institute for Health and Care Research Biomedical Research Centre Pregnancy and Prematurity Theme. G.D.S.C. is supported by the Genesis Research Trust. All authors report no direct conflict of interest. ISRCTN23947730. In recent years, interest has grown in clarifying t

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by aggregation of pathological tau. Recent advances in cryo-electron microscopy have enabled the classification of tauopathies at near-atomic resolution, revealing disease-specific tau filament conformations. These microstructural differences may influence the intracellular localization, intercellular propagation, and spatial distribution of tau pathology, as well as the microscopic binding profiles and macroscopic imaging signatures of tau positron emission tomography (PET) tracers. This review focuses on PSP by delineating its specific tau architecture and cellular and spatial distributions and how they differ in comparison with other major tauopathies and by critically discussing the clinical utility and limitations of tau PET. Through this integrative perspective, we aim to bridge neuropathological insights with in vivo PET findings. Engineered immunoglobulin M (IgM) antibodies typically exhibit superior neutralization potency and avidity compared to their parental IgG counterparts, primarily due to multivalent binding to repeated epitopes on a targeting antigen. In this study, we characterize the neutralization breadth and mechanism of action of IgM-14, a previously reported intranasally deliverable antibody targeting SARS-CoV-2. IgM-14 demonstrates remarkably potent antiviral activity against all pre-Omicron variants but significantly reduced efficacy against Omicron BA.1, and complete loss of activity against the later subvariant JN.1. Resistance selection identified two key mutations in the receptor-binding domain (RBD), G476D and F486P, which disrupt IgM-14 binding and confer strong resistance. Cryo-electron microscopy analysis uncovered two distinct Fab-RBD interfaces: a primary interface overlapping the angiotensin-converting enzyme 2 (ACE2)-binding region, and a unique secondary interface formed only when the RBD adopts the ACE2-inaccessible "down" conformation, involving a neighboring spike protomer. Site-directed mutagenesis and structural modeling revealed a critical role of this secondary site in IgM-14-mediated neutralization. Unlike IgG-14, structural modeling suggested that IgM-14 can simultaneously engage both interfaces in diverse modes, indicating a noncanonical avidity mechanism. Collectively, these findings highlight the structural and functional uniqueness of IgM-14 and offer valuable insights into the rational design of next-generation spike-targeted antibody therapeutics with enhanced breadth and potency. Retrograde transport is central to endomembrane homeostasis, yet the identity and origin of plant retrograde carriers remain unresolved. Prevailing models propose that plant vacuolar sorting receptors (VSRs) recycle either from multivesicular bodies (MVBs) to the trans-Golgi network (TGN) or from the TGN to the Golgi apparatus and/or endoplasmic reticulum (ER). However, the ultrastructural features of plant retrograde transport carriers remain largely unresolved. Here, we show that plant retrograde transport is likely mediated by a previously unrecognized class of MVB-derived spherical vesicles. Using correlative light and electron microscopy and three-dimensional electron tomography, we identify a distinct population of ~30-50 nm spherical vesicles adjacent to MVBs, including nascent vesicles budding from the MVB limiting membrane in Arabidopsis root cells. Immunogold labeling shows that these vesicles are enriched in retromer components and VSRs, suggesting that they possibly function as retrograde transport carriers. To investigate their biogenesis, we perform cryo-electron microscopy and liposome tubulation assays, showing that Arabidopsis SNX1 generates shorter membrane tubules than its mammalian counterpart, consistent with reduced membrane affinity linked to differences in the amphipathic helix. Notably, the SNX1-SNX2 heterodimer produces heterogeneous structures, including spherical vesicles, recapitulating in vivo observations. Lastly, knockdown of SNX1 or SNX2 results in vacuolar mislocalization and increased degradation of GFP-VSR2, and defects in SNX1 and VPS29 inhibit formation of spherical vesicles adjacent to MVBs, resulting in embryonic lethality before the globular stage. Together, these findings establish MVB-derived spherical vesicles as plant retrograde carriers and reveal a distinct SNX-mediated mechanism underlying their formation. To study the effect of embryo cryopreservation duration on pregnancy and neonatal outcomes in women transferred with high-quality blastocyst during frozen embryo transfer (FET) cycles. Multicenter Retrospective cohort study. Three tertiary-care academic medical centers. This retrospective study included a total of 24,101 women who underwent single high-quality blastocyst transfer during their first FET cycles at three tertiary academic medical centers between January 2016 and June 2023. Women were categorized into two groups according to the duration of embryo cryopreservation: the short Cryo group consisted of 23,933 women with a storage time of 0-5 years, while the long Cryo group included 168 women with a storage time > 5 years. Women in the long Cryo group were matched to those in the short Cryo group using propensity score matching with a 1:4 ratio. The pregnancy outcomes and the neonatal outcomes. After adjusting for potential confounding factors, no significant differences were observed between the two groups in pregnancy outcomes, including biochemical pregnancy (adjust odds ratio [aOR] 1.04, 95% confidence interval [CI], 0.70-1.56; P = 0.831), clinical pregnancy (aOR 1.10, 95% CI, 0.75-1.60; P = 0.638), ectopic pregnancy (aOR 2.15, 95% CI, 0.37-12.56; P = 0.394), miscarriage (aOR 0.95, 95% CI, 0.54-1.69; P = 0.871), and live birth (aOR 1.09, 95% CI, 0.76-1.55; P = 0.646). In addition, no significant differences were observed in neonatal outcomes, including very preterm birth, preterm birth, very low birth weight, low birth weight, high birth weight, birth weight, and gestational age. Our analysis found no evidence of significant associations between prolonged cryopreservation of high-quality blastocysts and adverse pregnancy or neonatal outcomes. Cfr methylates C 8 of adenosine 2503 (A2503) in 23 S ribosomal RNA (rRNA) and will also methylate C 2 of A2503 after methylating C 8 . C 8 methylation confers resistance to more than five classes of clinically used antibiotics, highlighting it as a worrisome mechanism of antibiotic resistance. Here, we report the structure of Cfr, determined by cryogenic electron microscopy (Cryo-EM). Despite its small size (∼36 kDa), we exploit a transient protein-RNA crosslink that forms during catalysis, which requires Cys105 to resolve. Using a Cfr Cys105Ala variant and an 87-nucleotide strand of rRNA, we isolate the crosslinked species and determine its structure to 3.0 Å resolution. Notably, the 87-mer rRNA adopts an L-shaped conformation characteristic of tRNAs, rather than the conformation it assumes in the ribosome. Cryo-EM structure of Cfr, a radical S-adenosylmethionine methylase that confers antibiotic resistance. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in metabolism, cell motility, development, and immune responses. Its dysregulation is linked to various diseases, including cancer, in which it can enhance tumor progression and suppress immune responses. High-resolution cryo-electron microscopy (cryo-EM) structures of the human cytosolic AHR complex have recently been solved and have provided insights into its agonist-binding mechanisms. However, our understanding of AHR antagonist binding remains limited. Our computational study, using the structure of the indirubin-bound human cytosolic AHR complex together with state-of-the-art docking algorithms and molecular dynamics simulations, suggests that AHR antagonists may bind either to the ligand-binding pocket or to alternative, as yet

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Fertilization ensures the transmission of genetic material across generations through a series of precisely coordinated physiological and molecular events. To fertilize an oocyte, a spermatozoon must pass through the cumulus cell layer, penetrate the zona pellucida (ZP), and ultimately adhere to and fuse with the oolemma (the oocyte plasma membrane). Upon fusion, the oocyte initiates mechanisms to block additional sperm entry at both the ZP and oolemma. These processes are highly dynamic in space and time, posing substantial technical barriers to their mechanistic dissection. Nonetheless, recent in silico, in vitro, and in vivo studies have begun to elucidate how intricate networks of intracellular signaling cascades and extracellular protein-protein interactions orchestrate successful fertilization in vertebrates. However, the extent to which these findings accurately reflect the biology of human sperm-oocyte interactions remains obscure, owing to ethical constraints on human gamete experimentation and the limited availability of patients harboring pathogenic variants in fertilization-related genes. This narrative review synthesizes current knowledge of the molecular determinants governing mammalian sperm-oocyte interactions, summarizes relevant genetic anomalies identified in infertile patients, and discusses emerging experimental approaches for the direct investigation of human fertilization. We also explore how recent mechanistic insights and technological innovations may inform the diagnosis and treatment of fertilization disorders and guide the development of novel contraceptive strategies. We searched PubMed, Google Scholar, and Scopus to identify research and review articles published in English. Studies limited to non-mammalian species and non-peer-reviewed preprints were excluded. Searches used terms related to fertilization, sperm-oocyte interactions, ZP, cumulus cells, polyspermy block, and human infertility, alone or in combination. Additional searches targeted key proteins and emerging technologies relevant to mammalian fertilization, clinical diagnostics, and contraceptive development. Our mechanistic understanding of mammalian gamete interactions has predominantly stemmed from in vitro and in vivo animal studies, which have revealed key molecular processes, such as sperm hyaluronidase-mediated cumulus matrix dispersal, translocation of sperm acrosomal membrane proteins to enable oolemma interaction, and ZP glycoprotein cleavage underlying the polyspermy block. While studies in model species remain indispensable, translating this knowledge to human biology requires meticulous validation. The integration of interdisciplinary approaches, such as humanized mouse models, artificial human oocytes, xenospecies fertilization assays, antibody inhibition studies, and high-throughput interactome screening, offers promising avenues to clarify interspecies discrepancies and generate insights more directly relevant to human gamete interactions. Advances in the mechanistic dissection of sperm-oocyte interactions are anticipated to support the development of diagnostic tools and therapeutic interventions for infertility caused by defective fertilization. In parallel, these discoveries may enable the rational design of safe, reversible contraceptives that selectively block gamete interactions without compromising other physiological processes. N/A. The compositional and structural heterogeneity of plasma HDL (high-density lipoprotein) underlies its multiple proposed cardioprotective functions. This review explores current ideas for how the structural diversity of HDL particles arises during their biogenesis through ABCA1 (ATP-binding cassette transporter A1)-mediated efflux of membrane phospholipids and cholesterol to APOA1 (apolipoprotein A1), HDL's major protein. The proposed mechanisms driving the formation of nascent HDL particles, varying in size and in the number of APOA1 and lipid molecules they contain, are described. Subsequent remodeling in the plasma compartment produces HDL subspecies with distinct sets of associated proteins. The role of differently sized HDL particles in promoting reverse cholesterol transport by t

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Fertilization ensures the transmission of genetic material across generations through a series of precisely coordinated physiological and molecular events. To fertilize an oocyte, a spermatozoon must pass through the cumulus cell layer, penetrate the zona pellucida (ZP), and ultimately adhere to and fuse with the oolemma (the oocyte plasma membrane). Upon fusion, the oocyte initiates mechanisms to block additional sperm entry at both the ZP and oolemma. These processes are highly dynamic in space and time, posing substantial technical barriers to their mechanistic dissection. Nonetheless, recent in silico, in vitro, and in vivo studies have begun to elucidate how intricate networks of intracellular signaling cascades and extracellular protein-protein interactions orchestrate successful fertilization in vertebrates. However, the extent to which these findings accurately reflect the biology of human sperm-oocyte interactions remains obscure, owing to ethical constraints on human gamete experimentation and the limited availability of patients harboring pathogenic variants in fertilization-related genes. This narrative review synthesizes current knowledge of the molecular determinants governing mammalian sperm-oocyte interactions, summarizes relevant genetic anomalies identified in infertile patients, and discusses emerging experimental approaches for the direct investigation of human fertilization. We also explore how recent mechanistic insights and technological innovations may inform the diagnosis and treatment of fertilization disorders and guide the development of novel contraceptive strategies. We searched PubMed, Google Scholar, and Scopus to identify research and review articles published in English. Studies limited to non-mammalian species and non-peer-reviewed preprints were excluded. Searches used terms related to fertilization, sperm-oocyte interactions, ZP, cumulus cells, polyspermy block, and human infertility, alone or in combination. Additional searches targeted key proteins and emerging technologies relevant to mammalian fertilization, clinical diagnostics, and contraceptive development. Our mechanistic understanding of mammalian gamete interactions has predominantly stemmed from in vitro and in vivo animal studies, which have revealed key molecular processes, such as sperm hyaluronidase-mediated cumulus matrix dispersal, translocation of sperm acrosomal membrane proteins to enable oolemma interaction, and ZP glycoprotein cleavage underlying the polyspermy block. While studies in model species remain indispensable, translating this knowledge to human biology requires meticulous validation. The integration of interdisciplinary approaches, such as humanized mouse models, artificial human oocytes, xenospecies fertilization assays, antibody inhibition studies, and high-throughput interactome screening, offers promising avenues to clarify interspecies discrepancies and generate insights more directly relevant to human gamete interactions. Advances in the mechanistic dissection of sperm-oocyte interactions are anticipated to support the development of diagnostic tools and therapeutic interventions for infertility caused by defective fertilization. In parallel, these discoveries may enable the rational design of safe, reversible contraceptives that selectively block gamete interactions without compromising other physiological processes. N/A. The compositional and structural heterogeneity of plasma HDL (high-density lipoprotein) underlies its multiple proposed cardioprotective functions. This review explores current ideas for how the structural diversity of HDL particles arises during their biogenesis through ABCA1 (ATP-binding cassette transporter A1)-mediated efflux of membrane phospholipids and cholesterol to APOA1 (apolipoprotein A1), HDL's major protein. The proposed mechanisms driving the formation of nascent HDL particles, varying in size and in the number of APOA1 and lipid molecules they contain, are described. Subsequent remodeling in the plasma compartment produces HDL subspecies with distinct sets of associated proteins. The role of differently sized HDL particles in promoting reverse cholesterol transport by t

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Fertilization ensures the transmission of genetic material across generations through a series of precisely coordinated physiological and molecular events. To fertilize an oocyte, a spermatozoon must pass through the cumulus cell layer, penetrate the zona pellucida (ZP), and ultimately adhere to and fuse with the oolemma (the oocyte plasma membrane). Upon fusion, the oocyte initiates mechanisms to block additional sperm entry at both the ZP and oolemma. These processes are highly dynamic in space and time, posing substantial technical barriers to their mechanistic dissection. Nonetheless, recent in silico, in vitro, and in vivo studies have begun to elucidate how intricate networks of intracellular signaling cascades and extracellular protein-protein interactions orchestrate successful fertilization in vertebrates. However, the extent to which these findings accurately reflect the biology of human sperm-oocyte interactions remains obscure, owing to ethical constraints on human gamete experimentation and the limited availability of patients harboring pathogenic variants in fertilization-related genes. This narrative review synthesizes current knowledge of the molecular determinants governing mammalian sperm-oocyte interactions, summarizes relevant genetic anomalies identified in infertile patients, and discusses emerging experimental approaches for the direct investigation of human fertilization. We also explore how recent mechanistic insights and technological innovations may inform the diagnosis and treatment of fertilization disorders and guide the development of novel contraceptive strategies. We searched PubMed, Google Scholar, and Scopus to identify research and review articles published in English. Studies limited to non-mammalian species and non-peer-reviewed preprints were excluded. Searches used terms related to fertilization, sperm-oocyte interactions, ZP, cumulus cells, polyspermy block, and human infertility, alone or in combination. Additional searches targeted key proteins and emerging technologies relevant to mammalian fertilization, clinical diagnostics, and contraceptive development. Our mechanistic understanding of mammalian gamete interactions has predominantly stemmed from in vitro and in vivo animal studies, which have revealed key molecular processes, such as sperm hyaluronidase-mediated cumulus matrix dispersal, translocation of sperm acrosomal membrane proteins to enable oolemma interaction, and ZP glycoprotein cleavage underlying the polyspermy block. While studies in model species remain indispensable, translating this knowledge to human biology requires meticulous validation. The integration of interdisciplinary approaches, such as humanized mouse models, artificial human oocytes, xenospecies fertilization assays, antibody inhibition studies, and high-throughput interactome screening, offers promising avenues to clarify interspecies discrepancies and generate insights more directly relevant to human gamete interactions. Advances in the mechanistic dissection of sperm-oocyte interactions are anticipated to support the development of diagnostic tools and therapeutic interventions for infertility caused by defective fertilization. In parallel, these discoveries may enable the rational design of safe, reversible contraceptives that selectively block gamete interactions without compromising other physiological processes. N/A. The compositional and structural heterogeneity of plasma HDL (high-density lipoprotein) underlies its multiple proposed cardioprotective functions. This review explores current ideas for how the structural diversity of HDL particles arises during their biogenesis through ABCA1 (ATP-binding cassette transporter A1)-mediated efflux of membrane phospholipids and cholesterol to APOA1 (apolipoprotein A1), HDL's major protein. The proposed mechanisms driving the formation of nascent HDL particles, varying in size and in the number of APOA1 and lipid molecules they contain, are described. Subsequent remodeling in the plasma compartment produces HDL subspecies with distinct sets of associated proteins. The role of differently sized HDL particles in promoting reverse cholesterol transport by t

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Fertilization ensures the transmission of genetic material across generations through a series of precisely coordinated physiological and molecular events. To fertilize an oocyte, a spermatozoon must pass through the cumulus cell layer, penetrate the zona pellucida (ZP), and ultimately adhere to and fuse with the oolemma (the oocyte plasma membrane). Upon fusion, the oocyte initiates mechanisms to block additional sperm entry at both the ZP and oolemma. These processes are highly dynamic in space and time, posing substantial technical barriers to their mechanistic dissection. Nonetheless, recent in silico, in vitro, and in vivo studies have begun to elucidate how intricate networks of intracellular signaling cascades and extracellular protein-protein interactions orchestrate successful fertilization in vertebrates. However, the extent to which these findings accurately reflect the biology of human sperm-oocyte interactions remains obscure, owing to ethical constraints on human gamete experimentation and the limited availability of patients harboring pathogenic variants in fertilization-related genes. This narrative review synthesizes current knowledge of the molecular determinants governing mammalian sperm-oocyte interactions, summarizes relevant genetic anomalies identified in infertile patients, and discusses emerging experimental approaches for the direct investigation of human fertilization. We also explore how recent mechanistic insights and technological innovations may inform the diagnosis and treatment of fertilization disorders and guide the development of novel contraceptive strategies. We searched PubMed, Google Scholar, and Scopus to identify research and review articles published in English. Studies limited to non-mammalian species and non-peer-reviewed preprints were excluded. Searches used terms related to fertilization, sperm-oocyte interactions, ZP, cumulus cells, polyspermy block, and human infertility, alone or in combination. Additional searches targeted key proteins and emerging technologies relevant to mammalian fertilization, clinical diagnostics, and contraceptive development. Our mechanistic understanding of mammalian gamete interactions has predominantly stemmed from in vitro and in vivo animal studies, which have revealed key molecular processes, such as sperm hyaluronidase-mediated cumulus matrix dispersal, translocation of sperm acrosomal membrane proteins to enable oolemma interaction, and ZP glycoprotein cleavage underlying the polyspermy block. While studies in model species remain indispensable, translating this knowledge to human biology requires meticulous validation. The integration of interdisciplinary approaches, such as humanized mouse models, artificial human oocytes, xenospecies fertilization assays, antibody inhibition studies, and high-throughput interactome screening, offers promising avenues to clarify interspecies discrepancies and generate insights more directly relevant to human gamete interactions. Advances in the mechanistic dissection of sperm-oocyte interactions are anticipated to support the development of diagnostic tools and therapeutic interventions for infertility caused by defective fertilization. In parallel, these discoveries may enable the rational design of safe, reversible contraceptives that selectively block gamete interactions without compromising other physiological processes. N/A. The compositional and structural heterogeneity of plasma HDL (high-density lipoprotein) underlies its multiple proposed cardioprotective functions. This review explores current ideas for how the structural diversity of HDL particles arises during their biogenesis through ABCA1 (ATP-binding cassette transporter A1)-mediated efflux of membrane phospholipids and cholesterol to APOA1 (apolipoprotein A1), HDL's major protein. The proposed mechanisms driving the formation of nascent HDL particles, varying in size and in the number of APOA1 and lipid molecules they contain, are described. Subsequent remodeling in the plasma compartment produces HDL subspecies with distinct sets of associated proteins. The role of differently sized HDL particles in promoting reverse cholesterol transport by t

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Fertilization ensures the transmission of genetic material across generations through a series of precisely coordinated physiological and molecular events. To fertilize an oocyte, a spermatozoon must pass through the cumulus cell layer, penetrate the zona pellucida (ZP), and ultimately adhere to and fuse with the oolemma (the oocyte plasma membrane). Upon fusion, the oocyte initiates mechanisms to block additional sperm entry at both the ZP and oolemma. These processes are highly dynamic in space and time, posing substantial technical barriers to their mechanistic dissection. Nonetheless, recent in silico, in vitro, and in vivo studies have begun to elucidate how intricate networks of intracellular signaling cascades and extracellular protein-protein interactions orchestrate successful fertilization in vertebrates. However, the extent to which these findings accurately reflect the biology of human sperm-oocyte interactions remains obscure, owing to ethical constraints on human gamete experimentation and the limited availability of patients harboring pathogenic variants in fertilization-related genes. This narrative review synthesizes current knowledge of the molecular determinants governing mammalian sperm-oocyte interactions, summarizes relevant genetic anomalies identified in infertile patients, and discusses emerging experimental approaches for the direct investigation of human fertilization. We also explore how recent mechanistic insights and technological innovations may inform the diagnosis and treatment of fertilization disorders and guide the development of novel contraceptive strategies. We searched PubMed, Google Scholar, and Scopus to identify research and review articles published in English. Studies limited to non-mammalian species and non-peer-reviewed preprints were excluded. Searches used terms related to fertilization, sperm-oocyte interactions, ZP, cumulus cells, polyspermy block, and human infertility, alone or in combination. Additional searches targeted key proteins and emerging technologies relevant to mammalian fertilization, clinical diagnostics, and contraceptive development. Our mechanistic understanding of mammalian gamete interactions has predominantly stemmed from in vitro and in vivo animal studies, which have revealed key molecular processes, such as sperm hyaluronidase-mediated cumulus matrix dispersal, translocation of sperm acrosomal membrane proteins to enable oolemma interaction, and ZP glycoprotein cleavage underlying the polyspermy block. While studies in model species remain indispensable, translating this knowledge to human biology requires meticulous validation. The integration of interdisciplinary approaches, such as humanized mouse models, artificial human oocytes, xenospecies fertilization assays, antibody inhibition studies, and high-throughput interactome screening, offers promising avenues to clarify interspecies discrepancies and generate insights more directly relevant to human gamete interactions. Advances in the mechanistic dissection of sperm-oocyte interactions are anticipated to support the development of diagnostic tools and therapeutic interventions for infertility caused by defective fertilization. In parallel, these discoveries may enable the rational design of safe, reversible contraceptives that selectively block gamete interactions without compromising other physiological processes. N/A. The compositional and structural heterogeneity of plasma HDL (high-density lipoprotein) underlies its multiple proposed cardioprotective functions. This review explores current ideas for how the structural diversity of HDL particles arises during their biogenesis through ABCA1 (ATP-binding cassette transporter A1)-mediated efflux of membrane phospholipids and cholesterol to APOA1 (apolipoprotein A1), HDL's major protein. The proposed mechanisms driving the formation of nascent HDL particles, varying in size and in the number of APOA1 and lipid molecules they contain, are described. Subsequent remodeling in the plasma compartment produces HDL subspecies with distinct sets of associated proteins. The role of differently sized HDL particles in promoting reverse cholesterol transport by t

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Fertilization ensures the transmission of genetic material across generations through a series of precisely coordinated physiological and molecular events. To fertilize an oocyte, a spermatozoon must pass through the cumulus cell layer, penetrate the zona pellucida (ZP), and ultimately adhere to and fuse with the oolemma (the oocyte plasma membrane). Upon fusion, the oocyte initiates mechanisms to block additional sperm entry at both the ZP and oolemma. These processes are highly dynamic in space and time, posing substantial technical barriers to their mechanistic dissection. Nonetheless, recent in silico, in vitro, and in vivo studies have begun to elucidate how intricate networks of intracellular signaling cascades and extracellular protein-protein interactions orchestrate successful fertilization in vertebrates. However, the extent to which these findings accurately reflect the biology of human sperm-oocyte interactions remains obscure, owing to ethical constraints on human gamete experimentation and the limited availability of patients harboring pathogenic variants in fertilization-related genes. This narrative review synthesizes current knowledge of the molecular determinants governing mammalian sperm-oocyte interactions, summarizes relevant genetic anomalies identified in infertile patients, and discusses emerging experimental approaches for the direct investigation of human fertilization. We also explore how recent mechanistic insights and technological innovations may inform the diagnosis and treatment of fertilization disorders and guide the development of novel contraceptive strategies. We searched PubMed, Google Scholar, and Scopus to identify research and review articles published in English. Studies limited to non-mammalian species and non-peer-reviewed preprints were excluded. Searches used terms related to fertilization, sperm-oocyte interactions, ZP, cumulus cells, polyspermy block, and human infertility, alone or in combination. Additional searches targeted key proteins and emerging technologies relevant to mammalian fertilization, clinical diagnostics, and contraceptive development. Our mechanistic understanding of mammalian gamete interactions has predominantly stemmed from in vitro and in vivo animal studies, which have revealed key molecular processes, such as sperm hyaluronidase-mediated cumulus matrix dispersal, translocation of sperm acrosomal membrane proteins to enable oolemma interaction, and ZP glycoprotein cleavage underlying the polyspermy block. While studies in model species remain indispensable, translating this knowledge to human biology requires meticulous validation. The integration of interdisciplinary approaches, such as humanized mouse models, artificial human oocytes, xenospecies fertilization assays, antibody inhibition studies, and high-throughput interactome screening, offers promising avenues to clarify interspecies discrepancies and generate insights more directly relevant to human gamete interactions. Advances in the mechanistic dissection of sperm-oocyte interactions are anticipated to support the development of diagnostic tools and therapeutic interventions for infertility caused by defective fertilization. In parallel, these discoveries may enable the rational design of safe, reversible contraceptives that selectively block gamete interactions without compromising other physiological processes. N/A. The compositional and structural heterogeneity of plasma HDL (high-density lipoprotein) underlies its multiple proposed cardioprotective functions. This review explores current ideas for how the structural diversity of HDL particles arises during their biogenesis through ABCA1 (ATP-binding cassette transporter A1)-mediated efflux of membrane phospholipids and cholesterol to APOA1 (apolipoprotein A1), HDL's major protein. The proposed mechanisms driving the formation of nascent HDL particles, varying in size and in the number of APOA1 and lipid molecules they contain, are described. Subsequent remodeling in the plasma compartment produces HDL subspecies with distinct sets of associated proteins. The role of differently sized HDL particles in promoting reverse cholesterol transport by t

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Fertilization ensures the transmission of genetic material across generations through a series of precisely coordinated physiological and molecular events. To fertilize an oocyte, a spermatozoon must pass through the cumulus cell layer, penetrate the zona pellucida (ZP), and ultimately adhere to and fuse with the oolemma (the oocyte plasma membrane). Upon fusion, the oocyte initiates mechanisms to block additional sperm entry at both the ZP and oolemma. These processes are highly dynamic in space and time, posing substantial technical barriers to their mechanistic dissection. Nonetheless, recent in silico, in vitro, and in vivo studies have begun to elucidate how intricate networks of intracellular signaling cascades and extracellular protein-protein interactions orchestrate successful fertilization in vertebrates. However, the extent to which these findings accurately reflect the biology of human sperm-oocyte interactions remains obscure, owing to ethical constraints on human gamete experimentation and the limited availability of patients harboring pathogenic variants in fertilization-related genes. This narrative review synthesizes current knowledge of the molecular determinants governing mammalian sperm-oocyte interactions, summarizes relevant genetic anomalies identified in infertile patients, and discusses emerging experimental approaches for the direct investigation of human fertilization. We also explore how recent mechanistic insights and technological innovations may inform the diagnosis and treatment of fertilization disorders and guide the development of novel contraceptive strategies. We searched PubMed, Google Scholar, and Scopus to identify research and review articles published in English. Studies limited to non-mammalian species and non-peer-reviewed preprints were excluded. Searches used terms related to fertilization, sperm-oocyte interactions, ZP, cumulus cells, polyspermy block, and human infertility, alone or in combination. Additional searches targeted key proteins and emerging technologies relevant to mammalian fertilization, clinical diagnostics, and contraceptive development. Our mechanistic understanding of mammalian gamete interactions has predominantly stemmed from in vitro and in vivo animal studies, which have revealed key molecular processes, such as sperm hyaluronidase-mediated cumulus matrix dispersal, translocation of sperm acrosomal membrane proteins to enable oolemma interaction, and ZP glycoprotein cleavage underlying the polyspermy block. While studies in model species remain indispensable, translating this knowledge to human biology requires meticulous validation. The integration of interdisciplinary approaches, such as humanized mouse models, artificial human oocytes, xenospecies fertilization assays, antibody inhibition studies, and high-throughput interactome screening, offers promising avenues to clarify interspecies discrepancies and generate insights more directly relevant to human gamete interactions. Advances in the mechanistic dissection of sperm-oocyte interactions are anticipated to support the development of diagnostic tools and therapeutic interventions for infertility caused by defective fertilization. In parallel, these discoveries may enable the rational design of safe, reversible contraceptives that selectively block gamete interactions without compromising other physiological processes. N/A. The compositional and structural heterogeneity of plasma HDL (high-density lipoprotein) underlies its multiple proposed cardioprotective functions. This review explores current ideas for how the structural diversity of HDL particles arises during their biogenesis through ABCA1 (ATP-binding cassette transporter A1)-mediated efflux of membrane phospholipids and cholesterol to APOA1 (apolipoprotein A1), HDL's major protein. The proposed mechanisms driving the formation of nascent HDL particles, varying in size and in the number of APOA1 and lipid molecules they contain, are described. Subsequent remodeling in the plasma compartment produces HDL subspecies with distinct sets of associated proteins. The role of differently sized HDL particles in promoting reverse cholesterol transport by t

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Early defibrillation using an automated external defibrillator (AED) is a key determinant of survival after out-of-hospital cardiac arrest (OHCA). However, the impact of clothing removal strategies on time to defibrillation and AED pad placement accuracy remains unclear. We conducted a prospective, randomized controlled simulation trial involving 40 undergraduate students without healthcare provider-level resuscitation training. Participants were randomly assigned (1:1) to the scissors or no-scissors group during a simulated OHCA scenario using a clothed manikin. The primary outcome was time from AED power-on to shock delivery. The secondary outcome was AED pad placement accuracy evaluated using standardized anatomical criteria. The median time from AED power-on to shock delivery was longer in the scissors group than in the no-scissors group (118 vs 91.5 s; Hodges-Lehmann median difference 24 s, 95% CI 6-39; p = 0.004). The AED pad placement accuracy did not differ between groups (anterior pad: OR 1.00, 95% CI 0.13-7.89; lateral pad: OR 0.67, 95% CI 0.19-2.33). Overall, the correct pad placement rates were low in both groups (10% anterior, 55% lateral). In this randomized controlled simulation trial, the use of scissors for clothing removal was associated with a longer time from AED power-on to shock delivery, without improvement in pad placement accuracy. These findings do not support routine scissor use under the simulated conditions. Larger studies are needed to determine the role of clothing removal strategies in AED training for lay rescuers. To investigate the clinical relevance of plasma plasminogen activator inhibitor-1 (PAI-1) in pediatric epilepsy, focusing on its associations with seizure severities and therapeutic outcomes. We conducted a prospective cohort study to compare the plasma PAI-1 levels quantified by ELISA across children with active epilepsy, seizure-free patients, and healthy controls. Furthermore, subgroup analyses were conducted to assess the impact of AED treatment or long-term drug response to the plasma PAI-1 levels. PAI-1 levels were 2.1-fold higher in the seizure group than in the control group (p < 0.0001), and 1.3-fold higher than in remission patients (p < 0.0001). No significant difference was observed between the anti-epileptic drug-treated and untreated subgroups (p = 0.0689). Baseline PAI-1 levels predicted 12-month pharmaco-responses, with pharmaco-resistant patients showing 12% higher PAI-1 concentrations than responders (p = 0.0234). Our findings establish plasma PAI-1 as a promising biomarker for identifying children at high risk for pharmaco-resistant epilepsy, thereby addressing a high-burden condition. The persistence of PAI-1 elevation hints at underlying inflammatory or synaptic pathologies that may be novel therapeutic targets beyond conventional AEDs. Recent evidence has demonstrated a tight relationship between neuronal activity and glioblastoma (GBM) growth, involving novel mechanisms such as neuron-glioma synapses and tumor microtube networks. Seizure activity and antiepileptic drug (AED) usage are highly prevalent among GBM patients. In this study, we investigate the impact of AEDs and their mechanism of action on overall survival (OS) in a cohort of patients treated for GBM. We performed a retrospective, single-center study of a cohort of histopathologically proven GBM patients at a tertiary center. Multivariate analyses were performed at 4 different timepoints by (1) patients who did and did not use AEDs, (2) use of individual AEDs, and (3) use of AEDs with the same mechanism of action. A total of 236 patients were included in the analysis, 178 of which were on anti-epileptics (75.4%). There was no significant impact of AEDs overall in OS-median survival was 16.2 months for patients taking AEDs and 13.8 months for patients not. Being on a voltage-gated sodium channel (VGNC) blocker seemed to confer a significant survival advantage at 24 months when compared with patients not on AEDs (hazard ratio [HR] = 0.67, P = .045). This significance was, however, lost when corrected for covariates (multivariable HR = 1.01, confidence interval [CI] = 0.67-1.54, P = .953). While patients on adjuvant treatment had a higher OS, this was only the case in patients -taking AEDs. There was no significant effect of AEDs on OS, VGNC blockers trended toward significance at 24 months. However, a link may exist between AEDs and the impact of adjuvant treatments. Epilepsy is a clinically significant neurological disorder requiring lifelong pharmacotherapy with antiepileptic drugs (AEDs). Precise quantification of these agents in pharmaceutical formulations and biological matrices is essential to ensure therapeutic efficacy and patient safety. Although high-performance liquid chromatography (HPLC) is the gold standard for AED determination, hydrophilic interaction liquid chromatography (HILIC) has emerged as a powerful alternative, especially for highly polar and hydrophilic AEDs. HILIC provides several advantages, including superior peak resolution, enhanced reproducibility, and reduced analysis time; yet, its application in AED analysis remains relatively underexplored. This review critically evaluates the literature regarding HILIC's application in this field, focusing on chromatographic parameters, detection strategies, and method validation. Emphasis is placed on analytical performance, specifically sensitivity, accuracy, precision, and speed. Collectively, the evidence underscores HILIC's potential as a robust and efficient platform for the routine monitoring and quality control of AEDs, highlighting an underutilized approach to enhancing AED determination. However, technical constraints, including prolonged column equilibration and the complexity of retention mechanisms, remain challenges for its widespread routine implementation. Immediate cardiopulmonary resuscitation and early defibrillation are key determinants of survival after out-of-hospital cardiac arrest (OHCA). Public access defibrillation (PAD) remains inconsistently implemented, with major gaps in automated external defibrillator (AED) availability, integration and use. This study aimed to identify and prioritise barriers and enablers to PAD implementation and to highlight emerging deployment models for future research. During the third International Community First Responder Symposium (April 2024, Hinterzarten, Germany), 46 experts from 14 countries participated in a structured RAND-UCLA Appropriateness Method consensus study. In moderated discussions, participants identified barriers and enablers to PAD, which were grouped into four thematic fields: availability and accessibility, usability and awareness, technological and systemic aspects, and financial and maintenance concerns. Nine statements were formulated and rated on a 9-point Likert scale; strong consensus was defined a priori as a median ≥ 7 with ≥ 80% of ratings in the 7-9 range. All nine statements met criteria for strong consensus. Key barriers included limited 24/7 AED access, poor coverage in residential areas, lack of centralised, real-time AED registries, insufficient public training and awareness, legal concerns for lay responders, patchy integration with emergency medical services, and device and maintenance costs. Key enablers comprised mandatory AED registration and live mapping, community training, legal protection for lay users, equipping police and fire services with AEDs within a "nearest vehicle" strategy, and improved data sharing between AEDs and hospitals. Experts also highlighted innovative deployment concepts, including use of postal and transport fleets, Vertical Take off and Landing drones, predictive positioning models and low-cost device designs. This international consensus study underscores the need for coordinated policy, robust AE

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Sclerotic bone lesions pose a significant diagnostic challenge due to their low diagnostic yield in core needle biopsy. In this technical note, we propose a novel modification to the standard biopsy technique aimed at improving the diagnostic yield of biopsies performed on sclerotic bone lesions. The modification involves use of trephine needle to acquire one bony core sample then using trucut biopsy needle to acquire samples through the tunnel created by the trephine needle. Our approach leverages optimized instrumentation to increase the likelihood of obtaining sufficient and representative tissue samples from challenging sclerotic lesions. Through a detailed description of the technique and its application in clinical practice, we demonstrate how this modification can significantly improve the diagnostic approach for sclerotic bone lesions, providing clinicians with a reliable method for accurate histopathological diagnosis. Robot-assisted, monoplane C-arm angiography systems designed for hybrid operating rooms represent an alternative approach to neuroendovascular procedures. Conversely, non-computer-assisted monoplane systems or conventional biplane systems in angiography suites are widely established. This study aims to evaluate the effectiveness, safety and efficiency of a robotic C-arm angiography system in performing neuroendovascular interventions, including cerebrovascular digital subtraction angiography (DSA), embolization of the middle meningeal artery (MMA) in subdural hematoma, and mechanical thrombectomy for vessel occlusion. All patients undergoing DSA, MMA embolization, or mechanical thrombectomy between July 2020 and December 2024 were retrospectively included. Procedures were performed using a monoplane robotic C-arm system (ARTIS pheno, Siemens Healthineers, Munich, Germany) in a hybrid operating room. Clinical data, procedural details, and imaging outcomes were analyzed. Radiation exposure was assessed by fluoroscopy time, air kerma, and dose-area product (DAP). A total of 49 procedures were analyzed, including 28 DSAs, 6 MMA embolizations, and 15 mechanical thrombectomies. DSA and MMA embolization (EMMA grade ≥2) achieved 100% procedural success, while mechanical thrombectomies achieved successful reperfusion (mTICI ≥2b) in 93.3% of cases. Median procedure durations were 34.0 (IQR 18.0-45.0) minutes for DSA, 70.0 (IQR 28.0-126.0) minutes for MMA embolization, and 84.0 (IQR 67.0-106.0) minutes for mechanical thrombectomy. Median fluoroscopy times were 5.2 (IQR 2.9-11.5) minutes (DSA), 21.3 (IQR 8.8-36.5) minutes (MMA embolization), and 21.2 (IQR 18.5-42.9) minutes (mechanical thrombectomy). Median DAPs were 7262.5 (IQR 3867.8-11570.8) µGy·m² (DSA), 16135.5 (IQR 8244.2-18216.2) µGy·m² (MMA embolization), and 9875.2 (IQR 6524.3-18455.5) µGy·m² (mechanical thrombectomy). Additional 3D-angiography or cone-beam CT (CBCT) was associated with higher radiation exposure. Basic neuroendovascular procedures can be safely and efficiently performed using a monoplane robotic C-arm in a hybrid operating room, achieving procedural success and radiation exposure levels comparable to conventional biplane systems. The purpose of this work was to commission and validate GPUMCD, a GPU-accelerated Monte Carlo dose calculation engine for c-arm Elekta linear accelerators (linac). This algorithm was recently released for clinical implementation in the Elekta One Treatment Planning System (v6.2.3, EOP). A GPUMCD beam model was generated for all photon energies of a VersaHD linac (6X, 6FFF, 10X, 10FFF, 18X). A validated version of the Monaco Commissioning Utility was used to compare calculated percent depth dose (PDD) profiles as well as lateral profiles for open fields against measurements. An adapted MPPG 5.b methodology was used to verify point-doses and 3D dose distributions in homogeneous and heterogeneous media using the ArcCheck, solid water, the CIRS ZEUS phantom, and the IROC HN and spine phantoms. The average agreement between measured and calculated PDDs and beam profiles using a local 2% dose difference (DD) in the high dose region for fields greater than 5 × 5 cm2 was 98.4% ± 2.3% for all energies. Using a 2% DD and 2 mm distance-to-agreement (DTA) gamma criteria for all fields using a 5% dose threshold yielded an agreement of 99.9% ± 0.5%. For open fields, GPUMCD reduced the calculation time by 93% as compared to X-ray voxel Monte Carlo (XVMC) using the same hardware. All MPPG 5.b. recommended testing was within the suggested tolerance limits. All plan measurements passed at the recommended gamma criteria. GPUMCD heterogeneity agreement and point dose measurements were found to agree within 3%. The GPUMCD algorithm in EOP was successfully tested and commissioned for clinical use for the VersaHD linac. Craniospinal irradiation (CSI) is a critical treatment modality for central nervous system (CNS) tumors. This study aimed to compare the dose-volume parameters and treatment efficiency between O-ring and C-arm linear accelerators (linacs) for CSI. A systematic search of English and Chinese databases was conducted from January 2005 to January 2026. Studies were evaluated using the PICOS framework. Data extraction and meta-analysis were performed using Stata 18.0 software encompassing subgroup analysis. Twelve studies involving 87 patients were included. No significant differences were found in dose to the planning target volume (PTV) between O-ring and C-arm linacs (Dmax: standardized mean difference (SMD) = -0.14, 95% confidence interval (CI): -0.61 to 0.32; Dmean: SMD = -0.53, 95% CI: -1.57 to 0.50). However, O-ring linacs, including dual-layer multi-leaf collimator linacs (DLM-linac) and helical radiotherapy (HR), delivered significantly lower maximum doses (Dmax) to the heart and liver (heart Dmax: SMD = -1.53, 95% CI: -2.53 to -0.52, p = 0.003; liver Dmax: SMD = -1.33, 95% CI: -2.29 to -0.37, p = 0.007). Subgroup analysis revealed that DLM-linac significantly reduced Dmax to the eyes and esophagus compared to C-arm linacs (eyes Dmax: SMD = -0.62, 95% CI: -1.22 to -0.01, p = 0.045; esophagus, Dmax: SMD = -0.45, 95% CI: -0.89 to -0.01, p = 0.044). Additionally, HR had the highest monitor units and the longest treatment time among all linac types. Both O-ring and C-arm linacs are effective for CSI. No significant difference in PTV dose was revealed when the doses to the lungs and thyroid are comparable. However, O-ring linacs, particularly DLM-linac, provide superior protection for critical organs such as eyes and esophagus without extending treatment time. Considering both dose advantage and treatment efficiency, DLM-linac is a suitable radiotherapy treatment modality for CSI. Non-traumatic atlantoaxial dislocation (AAD) is an uncommon condition characterized by abnormal displacement between the C1 and C2 vertebrae, resulting in upper cervical spine instability with the possibility of causing mortal injury. We report a 63-year-old woman presented with chronic mechanical occipitocervical pain and mild upper-extremity weakness lasting more than 20 years. Her vital signs and systematic examination were unremarkable. Neurological examination revealed mild weakness of upper-extremity weakness (grade 4/5), hyperreflexia, impaired fine motor control, hand numbness, and a positive dynamic Hoffmann sign. Preoperative CT-angiography demonstrated left vertebral artery hypoplasia and right high-riding vertebral artery associated with atlantoaxial dislocation. The patient underwent C1-C2 fusion using a hybrid construct: a C1 lateral mass screw and C2 translaminar screw on the HRVA side, and a transarticular screw on the contralateral side. Intraoperative neuromonitoring was unavailable; therefore, the procedure was guided carefully using real-time C-arm

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

Effective pain management is essential in veterinary needle-related procedures. Traditional methods, including infiltrative, cream, and spray formulations, have limitations such as delayed onset, inconsistent temperature control, and skin damage. This study evaluated the efficacy of a novel vapocoolant spray (VetEase®, Recensemedical, Hwaseong-si, Republic of Korea) for enhanced pain relief. Ninety cases of dogs received cryoanesthesia immediately before undergoing three types of needle-related procedures: centesis (including cystocentesis, thoracentesis, and abdominocentesis), fine-needle aspiration (FNA), and jugular venipuncture. Each procedure was divided into three groups based on cryoanesthesia spray conditions: control (no spray), group A (2 s at 2°C), and group B (5 s at 2°C). Modified pain scores and visual analog scale evaluations were recorded immediately after needle insertion to assess the reduction in pain. Pain evaluation criteria included vocalization, general movements, and other observable responses. Significant pain reduction was observed in the centesis procedure for the group treated with cryoanesthesia at 2°C for 5 s (Group B), with a mean modified pain score of 0.8 compared to 3.7 in the control group (p = 0.001). The visual analog scale also showed a significant reduction in Group B (p = 0.001). Although both cryoanesthesia groups showed reduced pain levels during FNA and jugular venipuncture procedures, the differences did not reach statistical significance. No skin complications were reported. The novel cryoanesthetic device significantly alleviated needle-related pain during centesis procedures in dogs. It provided rapid local anesthesia, eliminating the need for prolonged onset times and minimizing skin complications, thereby presenting a viable alternative to topical anesthetics. With the growing number of veterinary centers performing pacemaker implantation in small animals, a better understanding of anesthetic management of these procedures has become essential. Most available studies focus primarily on surgical techniques, with limited discussion of anesthetic safety, efficacy, and intraoperative complications. Eighteen anesthetic procedures for transvenous pacemaker implantation were retrospectively reviewed in dogs treated at a veterinary referral center in São Paulo, Brazil, between 2024 and 2025. All dogs underwent clinical and laboratory evaluation, electrocardiography and/or Holter monitoring, and echocardiography. Continuous intraoperative monitoring included heart rate, electrocardiography, respiratory rate, end-tidal CO2, oxygen saturation, temperature, and invasive or non-invasive arterial blood pressure. Collected data included age, breed, sex, anesthetic protocol, clinical conditions, intraoperative events, and outcomes. Continuous variables were expressed as mean ± SD or median (range) according to data distribution assessed by the Shapiro-Wilk test. Group comparisons were performed using Student's t-test or Mann-Whitney U test, and categorical variables were analyzed using chi-square or Fisher's exact test (p < 0.05). Sixteen dogs (8 males and 8 females) underwent 18 anesthetic procedures, including two reinterventions. The main indication for pacemaker implantation was third-degree atrioventricular block (75%). Anesthetic protocols were individualized according to patient comorbidities. The most frequent anesthetic complication was hypotension (27.7%), successfully managed with fluid therapy and vasoactive support. Electrode migration occurred in 11% of procedures and required reintervention. No perioperative deaths were recorded. Transvenous pacemaker implantation in dogs was successfully performed under individualized anesthetic management despite heterogeneous clinical conditions and absence of a standardized protocol. Hypotension was the most common anesthetic complication but was effectively treated. The routine use of temporary external pacing provided an essential safety margin for maintaining perioperative hemodynamic stability. No perioperative deaths were recorded. These findings support the feasibility and safety of tailored anesthetic strategies for canine pacemaker implantation, although prospective studies with larger populations are warranted to define optimal standardized protocols. This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO2 ablative fractional laser combined with intense pulsed light (CO2AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy. In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO2AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports. Both BTX-A and CO2AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (p < 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups. Both BTX-A and CO2AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO2AFL-IPL serving as an effective alternative where laser therapy is available. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . This study aimed to evaluate the feasibility of incorporating injectable platelet-rich fibrin (i-PRF) into electrospun chitosan-polyvinyl alcohol (PVA) nanofibers by assessing (1) swelling behavior after immersion in i-PRF, (2) potential interactions between components based on Fourier transform infrared spectroscopy (FTIR) profiles, and (3) initial in vitro cytocompatibility using human primary fibroblasts.Chitosan-PVA nanofibers were fabricated by electrospinning and trimmed into 5-mm discs. Specimens were immersed in 0.5 mL of i-PRF for six time points (5, 10, 15, 20, 25, and 30 minutes), and swelling capacity was evaluated to determine the immersion time associated with the highest absorption. FTIR was performed to compare functional group profiles before and after i-PRF immersion. For cytocompatibility testing, 5-mm diameter nanofiber discs were soaked in 0.5-mL i-PRF for 10 minutes and placed into wells seeded with human primary fibroblasts (5 × 103 cells/well). After 24, 48, and 72-hour incubation at 37°C in a CO2 incubator, methylthiazol tetrazolium (MTT) reagent was added and incubated for an additional 4 hours. Absorbance was measured using a multimode microplate reader, and cell viability was calculated as the percentage relative to the control group.The highest swelling was observed after 10 minutes of immersion (p < 0.05). FTIR spectra showed no additional peaks indicative of new chemical functional groups after immersion, suggesting that i-PRF incorporation occurred predominantly through physical interaction rather than formation of new covalent bonds. In the MTT assay, fibroblast viability in the i-PRF-immersed nanofiber group was comparable to the control (p < 0.05), indicating no detectable cytotoxic effect under the tested conditions.Chitosan-PVA nanofibers demonstrated an ability to absorb i-PRF, exhibiting comparable FTIR functional groups following immersion. This finding indicates that the pr

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. A 20-year-old female patient ingested approximately 1200 mL of antifreeze and was found comatose five hours later, after which she was transported to the hospital. On admission, she was in deep coma with respiratory failure and severe metabolic acidosis (pH 6.82). Laboratory findings revealed a high anion gap, elevated lactate levels, and acute kidney injury. Chest computed tomography (CT) showed aspiration pneumonia. Based on clinical history and examination, a diagnosis of ethylene glycol poisoning complicated by toxic encephalopathy and multiple organ dysfunction syndrome (MODS) was established. The patient received gastric lavage, ethanol antidote therapy, combined hemoperfusion and continuous renal replacement therapy (CRRT), as well as multi-organ supportive treatment. Mechanical ventilation was withdrawn on day 4, she was transferred to a general ward on day 6, and discharged on day 28 after recovery of renal function. This case highlights that early recognition of ethylene glycol poisoning, together with combined detoxification, blood purification, and organ support therapy, is essential for improving patient outcomes. Tracheal schwannoma is a rare benign tumor originating from Schwann cells, and it is even less common in adolescents. The clinical manifestations are usually nonspecific respiratory symptoms such as cough and sputum production, which can easily be mistaken for infectious diseases. Imaging findings often suggest an inflammatory mass, making early diagnosis challenging. A 15-year-old female was admitted with a 3-day history of cough and sputum production and was initially diagnosed with community-acquired pneumonia. High-resolution chest CT and 3D reconstruction revealed a well-defined, mildly to moderately enhanced round nodule (approximately 1.1 × 0.7 cm) in the lower trachea, accompanied by bronchopneumonia. Imaging findings suggested an inflammatory myofibroblastic tumor or inflammatory granuloma. The lesion was completely resected under painless bronchoscopy. Histopathology showed spindle cells arranged in bundles, with strong positive staining for S-100 and SOX-10 and a Ki-67 proliferation index of about 5%, confirming the diagnosis of benign tracheal schwannoma. After postoperative anti-infective therapy, the patient's symptoms rapidly resolved. Although tracheal schwannoma is benign, it may initially present as pneumonia and mimic an inflammatory tumor on imaging, leading to diagnostic confusion. For adolescent patients with recurrent respiratory symptoms and poor response to conventional therapy, early chest CT and bronchoscopy should be considered. Bronchoscopic resection combined with anti-infective therapy can achieve excellent outcomes. Neisseria gonorrhoeae (NG) causes sexually transmitted hyperacute bacterial conjunctivitis. Involvement of the lacrimal gland is exceedingly rare and has been previously reported in two case reports. This report discusses a 71-year-old male who presented with a painful red left eye. There was notable swelling of the upper eyelid, which was confirmed on CT to be due to lacrimal gland inflammation. Clinical features of dacryoadenitis associated with scleritis were found on ophthalmologic assessment. Conjunctival swabs were sent for culture and returned positive for NG, following which the patient reported a new sexual encounter previously unknown to the treating clinicians. Following IV ceftriaxone and flucloxacillin, topical steroid and chloramphenicol eye drops, the patient saw marked clinical improvement. This case demonstrates that NG may present with unusual features, and clinicians should have a low threshold for conjunctival cultures and promptly explore the sexual and social histories of patients presenting with similar symptomology. Isolated epididymal tuberculosis presenting as chronic hydrocele is exceptionally rare and poses significant diagnostic challenges. We report a healthy 35-year-old male who presented with 6-month progressive unilateral scrotal swelling clinically diagnosed as chronic hydrocele. During hydrocelectomy, intraoperative findings revealed approximately 150 mL of clear fluid with dense adhesions between testis and tunica vaginalis-an atypical finding that prompted epididymal biopsy. Histopathology demonstrated non-necrotizing granulomatous inflammation with epithelioid cells and multinucleated giant cells, suggestive of tuberculosis. Subsequent pulmonary evaluation confirmed active tuberculosis with positive sputum acid-fast bacilli (2 + on Ziehl-Neelsen stain), Mycobacterium tuberculosis detection by GeneXpert MTB/RIF, bilateral apical nodules with tree-in-bud opacities on chest CT, and 18 mm tuberculin skin test induration. The patient completed nine months of standard anti-tuberculosis therapy comprising intensive phase (rifampicin, isoniazid, pyrazinamide, ethambutol for two months) followed by continuation phase (rifampicin and isoniazid for seven months) with complete clinical and radiological resolution. This case highlights three critical diagnostic challenges: atypical presentation as isolated hydrocele without classic tuberculous features, non-necrotizing rather than typical caseating granulomas, an

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function. Understanding age‐related changes of brain function during aging in ASD is crucial to establish best practices for cognitive and health screenings to detect potential accelerated decline in older adults with ASD and to develop interventions that might reduce risk. BSV is an MRI‐based measure that decreases in typical aging and is linked to cognitive decline. In this study, we found that BSV decreases may occur earlier in 40–70‐year old adults with ASD compared to their neurotypical peers, possibly indicating accelerated aging, although additional longitudinal analyses will be required to confirm this. Verbal memory tasks differ in their cognitive demands and may rely on distinct left medial temporal structures. One model holds that verbal delayed recall is hippocampal dependent, whereas verbal paired associate learning relies on adjacent rhinal cortex. We test this by examining the relationship between task performance and regional temporal lobe volumes in individuals with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Retrospective analysis of 99 surgically naïve TLE patients (12 bilateral TLE-HS, 35 left TLE-HS, 28 right TLE-HS, and 24 MRI-negative left TLE) with contemporaneous neuropsychological and T1-weighted MRI data. Delayed recall was operationalized using the Rey Auditory Verbal Learning Test, and arbitrary associative learning with the Paired Associates Learning subtest. Linear regressions assessed associations between memory performance and temporal lobe volumes. We also studied a cohort with nonlesional left TLE to better distinguish the relative impact on verbal memory of left temporal onset seizures versus the structural integrity of the left mesial temporal lobe. Patients with left-sided TLE-HS (unilateral/bilateral) performed significantly worse on both memory measures compared to right TLE-HS and MRI-negative left TLE (p < 0.001). Left hippocampal volume significantly predicted performance on both measures (both p < 0.001), whereas rhinal cortex volumes were not significantly associated with either. Secondary analyses revealed associations between left temporal pole volume and both memory measures, and between inferior temporal gyrus volume and delayed recall. Despite differing cognitive demands, both verbal arbitrary associative learning and delayed recall were primarily linked to left hippocampal volume, underscoring its central role in verbal memory impairment in TLE. Associations with the temporal pole and inferior temporal regions suggest additional contributions from extrahippocampal areas. Left hippocampal atrophy exacerbates verbal memory impairment beyond what would be expected from seizure activity alone. The results of this study show that the ability to learn semantically unrelated information and recall unstructured information after a period of delay is particularly compromised in individuals with left hippocampal atrophy. These impairments were strongly associated with reduced left hippocampal volume. In contrast, volumes of the adjacent rhinal cortex were not related to memory performance. These findings underscore the central role of the left hippocampus in supporting verbal memory in temporal lobe epilepsy. This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Given that there are 27 bone stress injury (BSI) severity classification and scoring systems described in the literature, most systems are based solely on imaging, while the literature stresses the importance of considering clinical risk factors for return to running. To propose a modified BSI classification score incorporating clinical factors, bone location, Fredericson and Nattiv magnetic resonance imaging (MRI) grading systems, and bone type to improve prediction of return-to-running times. Cohort study; Level of evidence, 2. A 7-year prospective study of National Collegiate Athletic Association Division I cross-country and track and field athletes was conducted from 2013 to 2020. Participants completed an annual questionnaire about known risk factors for injury or impaired bone health. Information about BSIs and time to return to running was collected at team physician meeti

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function. Understanding age‐related changes of brain function during aging in ASD is crucial to establish best practices for cognitive and health screenings to detect potential accelerated decline in older adults with ASD and to develop interventions that might reduce risk. BSV is an MRI‐based measure that decreases in typical aging and is linked to cognitive decline. In this study, we found that BSV decreases may occur earlier in 40–70‐year old adults with ASD compared to their neurotypical peers, possibly indicating accelerated aging, although additional longitudinal analyses will be required to confirm this. Verbal memory tasks differ in their cognitive demands and may rely on distinct left medial temporal structures. One model holds that verbal delayed recall is hippocampal dependent, whereas verbal paired associate learning relies on adjacent rhinal cortex. We test this by examining the relationship between task performance and regional temporal lobe volumes in individuals with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Retrospective analysis of 99 surgically naïve TLE patients (12 bilateral TLE-HS, 35 left TLE-HS, 28 right TLE-HS, and 24 MRI-negative left TLE) with contemporaneous neuropsychological and T1-weighted MRI data. Delayed recall was operationalized using the Rey Auditory Verbal Learning Test, and arbitrary associative learning with the Paired Associates Learning subtest. Linear regressions assessed associations between memory performance and temporal lobe volumes. We also studied a cohort with nonlesional left TLE to better distinguish the relative impact on verbal memory of left temporal onset seizures versus the structural integrity of the left mesial temporal lobe. Patients with left-sided TLE-HS (unilateral/bilateral) performed significantly worse on both memory measures compared to right TLE-HS and MRI-negative left TLE (p < 0.001). Left hippocampal volume significantly predicted performance on both measures (both p < 0.001), whereas rhinal cortex volumes were not significantly associated with either. Secondary analyses revealed associations between left temporal pole volume and both memory measures, and between inferior temporal gyrus volume and delayed recall. Despite differing cognitive demands, both verbal arbitrary associative learning and delayed recall were primarily linked to left hippocampal volume, underscoring its central role in verbal memory impairment in TLE. Associations with the temporal pole and inferior temporal regions suggest additional contributions from extrahippocampal areas. Left hippocampal atrophy exacerbates verbal memory impairment beyond what would be expected from seizure activity alone. The results of this study show that the ability to learn semantically unrelated information and recall unstructured information after a period of delay is particularly compromised in individuals with left hippocampal atrophy. These impairments were strongly associated with reduced left hippocampal volume. In contrast, volumes of the adjacent rhinal cortex were not related to memory performance. These findings underscore the central role of the left hippocampus in supporting verbal memory in temporal lobe epilepsy. This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Given that there are 27 bone stress injury (BSI) severity classification and scoring systems described in the literature, most systems are based solely on imaging, while the literature stresses the importance of considering clinical risk factors for return to running. To propose a modified BSI classification score incorporating clinical factors, bone location, Fredericson and Nattiv magnetic resonance imaging (MRI) grading systems, and bone type to improve prediction of return-to-running times. Cohort study; Level of evidence, 2. A 7-year prospective study of National Collegiate Athletic Association Division I cross-country and track and field athletes was conducted from 2013 to 2020. Participants completed an annual questionnaire about known risk factors for injury or impaired bone health. Information about BSIs and time to return to running was collected at team physician meeti

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function. Understanding age‐related changes of brain function during aging in ASD is crucial to establish best practices for cognitive and health screenings to detect potential accelerated decline in older adults with ASD and to develop interventions that might reduce risk. BSV is an MRI‐based measure that decreases in typical aging and is linked to cognitive decline. In this study, we found that BSV decreases may occur earlier in 40–70‐year old adults with ASD compared to their neurotypical peers, possibly indicating accelerated aging, although additional longitudinal analyses will be required to confirm this. Verbal memory tasks differ in their cognitive demands and may rely on distinct left medial temporal structures. One model holds that verbal delayed recall is hippocampal dependent, whereas verbal paired associate learning relies on adjacent rhinal cortex. We test this by examining the relationship between task performance and regional temporal lobe volumes in individuals with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Retrospective analysis of 99 surgically naïve TLE patients (12 bilateral TLE-HS, 35 left TLE-HS, 28 right TLE-HS, and 24 MRI-negative left TLE) with contemporaneous neuropsychological and T1-weighted MRI data. Delayed recall was operationalized using the Rey Auditory Verbal Learning Test, and arbitrary associative learning with the Paired Associates Learning subtest. Linear regressions assessed associations between memory performance and temporal lobe volumes. We also studied a cohort with nonlesional left TLE to better distinguish the relative impact on verbal memory of left temporal onset seizures versus the structural integrity of the left mesial temporal lobe. Patients with left-sided TLE-HS (unilateral/bilateral) performed significantly worse on both memory measures compared to right TLE-HS and MRI-negative left TLE (p < 0.001). Left hippocampal volume significantly predicted performance on both measures (both p < 0.001), whereas rhinal cortex volumes were not significantly associated with either. Secondary analyses revealed associations between left temporal pole volume and both memory measures, and between inferior temporal gyrus volume and delayed recall. Despite differing cognitive demands, both verbal arbitrary associative learning and delayed recall were primarily linked to left hippocampal volume, underscoring its central role in verbal memory impairment in TLE. Associations with the temporal pole and inferior temporal regions suggest additional contributions from extrahippocampal areas. Left hippocampal atrophy exacerbates verbal memory impairment beyond what would be expected from seizure activity alone. The results of this study show that the ability to learn semantically unrelated information and recall unstructured information after a period of delay is particularly compromised in individuals with left hippocampal atrophy. These impairments were strongly associated with reduced left hippocampal volume. In contrast, volumes of the adjacent rhinal cortex were not related to memory performance. These findings underscore the central role of the left hippocampus in supporting verbal memory in temporal lobe epilepsy. This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Given that there are 27 bone stress injury (BSI) severity classification and scoring systems described in the literature, most systems are based solely on imaging, while the literature stresses the importance of considering clinical risk factors for return to running. To propose a modified BSI classification score incorporating clinical factors, bone location, Fredericson and Nattiv magnetic resonance imaging (MRI) grading systems, and bone type to improve prediction of return-to-running times. Cohort study; Level of evidence, 2. A 7-year prospective study of National Collegiate Athletic Association Division I cross-country and track and field athletes was conducted from 2013 to 2020. Participants completed an annual questionnaire about known risk factors for injury or impaired bone health. Information about BSIs and time to return to running was collected at team physician meeti

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function. Understanding age‐related changes of brain function during aging in ASD is crucial to establish best practices for cognitive and health screenings to detect potential accelerated decline in older adults with ASD and to develop interventions that might reduce risk. BSV is an MRI‐based measure that decreases in typical aging and is linked to cognitive decline. In this study, we found that BSV decreases may occur earlier in 40–70‐year old adults with ASD compared to their neurotypical peers, possibly indicating accelerated aging, although additional longitudinal analyses will be required to confirm this. Verbal memory tasks differ in their cognitive demands and may rely on distinct left medial temporal structures. One model holds that verbal delayed recall is hippocampal dependent, whereas verbal paired associate learning relies on adjacent rhinal cortex. We test this by examining the relationship between task performance and regional temporal lobe volumes in individuals with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Retrospective analysis of 99 surgically naïve TLE patients (12 bilateral TLE-HS, 35 left TLE-HS, 28 right TLE-HS, and 24 MRI-negative left TLE) with contemporaneous neuropsychological and T1-weighted MRI data. Delayed recall was operationalized using the Rey Auditory Verbal Learning Test, and arbitrary associative learning with the Paired Associates Learning subtest. Linear regressions assessed associations between memory performance and temporal lobe volumes. We also studied a cohort with nonlesional left TLE to better distinguish the relative impact on verbal memory of left temporal onset seizures versus the structural integrity of the left mesial temporal lobe. Patients with left-sided TLE-HS (unilateral/bilateral) performed significantly worse on both memory measures compared to right TLE-HS and MRI-negative left TLE (p < 0.001). Left hippocampal volume significantly predicted performance on both measures (both p < 0.001), whereas rhinal cortex volumes were not significantly associated with either. Secondary analyses revealed associations between left temporal pole volume and both memory measures, and between inferior temporal gyrus volume and delayed recall. Despite differing cognitive demands, both verbal arbitrary associative learning and delayed recall were primarily linked to left hippocampal volume, underscoring its central role in verbal memory impairment in TLE. Associations with the temporal pole and inferior temporal regions suggest additional contributions from extrahippocampal areas. Left hippocampal atrophy exacerbates verbal memory impairment beyond what would be expected from seizure activity alone. The results of this study show that the ability to learn semantically unrelated information and recall unstructured information after a period of delay is particularly compromised in individuals with left hippocampal atrophy. These impairments were strongly associated with reduced left hippocampal volume. In contrast, volumes of the adjacent rhinal cortex were not related to memory performance. These findings underscore the central role of the left hippocampus in supporting verbal memory in temporal lobe epilepsy. This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Given that there are 27 bone stress injury (BSI) severity classification and scoring systems described in the literature, most systems are based solely on imaging, while the literature stresses the importance of considering clinical risk factors for return to running. To propose a modified BSI classification score incorporating clinical factors, bone location, Fredericson and Nattiv magnetic resonance imaging (MRI) grading systems, and bone type to improve prediction of return-to-running times. Cohort study; Level of evidence, 2. A 7-year prospective study of National Collegiate Athletic Association Division I cross-country and track and field athletes was conducted from 2013 to 2020. Participants completed an annual questionnaire about known risk factors for injury or impaired bone health. Information about BSIs and time to return to running was collected at team physician meeti

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function. Understanding age‐related changes of brain function during aging in ASD is crucial to establish best practices for cognitive and health screenings to detect potential accelerated decline in older adults with ASD and to develop interventions that might reduce risk. BSV is an MRI‐based measure that decreases in typical aging and is linked to cognitive decline. In this study, we found that BSV decreases may occur earlier in 40–70‐year old adults with ASD compared to their neurotypical peers, possibly indicating accelerated aging, although additional longitudinal analyses will be required to confirm this. Verbal memory tasks differ in their cognitive demands and may rely on distinct left medial temporal structures. One model holds that verbal delayed recall is hippocampal dependent, whereas verbal paired associate learning relies on adjacent rhinal cortex. We test this by examining the relationship between task performance and regional temporal lobe volumes in individuals with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Retrospective analysis of 99 surgically naïve TLE patients (12 bilateral TLE-HS, 35 left TLE-HS, 28 right TLE-HS, and 24 MRI-negative left TLE) with contemporaneous neuropsychological and T1-weighted MRI data. Delayed recall was operationalized using the Rey Auditory Verbal Learning Test, and arbitrary associative learning with the Paired Associates Learning subtest. Linear regressions assessed associations between memory performance and temporal lobe volumes. We also studied a cohort with nonlesional left TLE to better distinguish the relative impact on verbal memory of left temporal onset seizures versus the structural integrity of the left mesial temporal lobe. Patients with left-sided TLE-HS (unilateral/bilateral) performed significantly worse on both memory measures compared to right TLE-HS and MRI-negative left TLE (p < 0.001). Left hippocampal volume significantly predicted performance on both measures (both p < 0.001), whereas rhinal cortex volumes were not significantly associated with either. Secondary analyses revealed associations between left temporal pole volume and both memory measures, and between inferior temporal gyrus volume and delayed recall. Despite differing cognitive demands, both verbal arbitrary associative learning and delayed recall were primarily linked to left hippocampal volume, underscoring its central role in verbal memory impairment in TLE. Associations with the temporal pole and inferior temporal regions suggest additional contributions from extrahippocampal areas. Left hippocampal atrophy exacerbates verbal memory impairment beyond what would be expected from seizure activity alone. The results of this study show that the ability to learn semantically unrelated information and recall unstructured information after a period of delay is particularly compromised in individuals with left hippocampal atrophy. These impairments were strongly associated with reduced left hippocampal volume. In contrast, volumes of the adjacent rhinal cortex were not related to memory performance. These findings underscore the central role of the left hippocampus in supporting verbal memory in temporal lobe epilepsy. This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Given that there are 27 bone stress injury (BSI) severity classification and scoring systems described in the literature, most systems are based solely on imaging, while the literature stresses the importance of considering clinical risk factors for return to running. To propose a modified BSI classification score incorporating clinical factors, bone location, Fredericson and Nattiv magnetic resonance imaging (MRI) grading systems, and bone type to improve prediction of return-to-running times. Cohort study; Level of evidence, 2. A 7-year prospective study of National Collegiate Athletic Association Division I cross-country and track and field athletes was conducted from 2013 to 2020. Participants completed an annual questionnaire about known risk factors for injury or impaired bone health. Information about BSIs and time to return to running was collected at team physician meeti

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function. Understanding age‐related changes of brain function during aging in ASD is crucial to establish best practices for cognitive and health screenings to detect potential accelerated decline in older adults with ASD and to develop interventions that might reduce risk. BSV is an MRI‐based measure that decreases in typical aging and is linked to cognitive decline. In this study, we found that BSV decreases may occur earlier in 40–70‐year old adults with ASD compared to their neurotypical peers, possibly indicating accelerated aging, although additional longitudinal analyses will be required to confirm this. Verbal memory tasks differ in their cognitive demands and may rely on distinct left medial temporal structures. One model holds that verbal delayed recall is hippocampal dependent, whereas verbal paired associate learning relies on adjacent rhinal cortex. We test this by examining the relationship between task performance and regional temporal lobe volumes in individuals with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Retrospective analysis of 99 surgically naïve TLE patients (12 bilateral TLE-HS, 35 left TLE-HS, 28 right TLE-HS, and 24 MRI-negative left TLE) with contemporaneous neuropsychological and T1-weighted MRI data. Delayed recall was operationalized using the Rey Auditory Verbal Learning Test, and arbitrary associative learning with the Paired Associates Learning subtest. Linear regressions assessed associations between memory performance and temporal lobe volumes. We also studied a cohort with nonlesional left TLE to better distinguish the relative impact on verbal memory of left temporal onset seizures versus the structural integrity of the left mesial temporal lobe. Patients with left-sided TLE-HS (unilateral/bilateral) performed significantly worse on both memory measures compared to right TLE-HS and MRI-negative left TLE (p < 0.001). Left hippocampal volume significantly predicted performance on both measures (both p < 0.001), whereas rhinal cortex volumes were not significantly associated with either. Secondary analyses revealed associations between left temporal pole volume and both memory measures, and between inferior temporal gyrus volume and delayed recall. Despite differing cognitive demands, both verbal arbitrary associative learning and delayed recall were primarily linked to left hippocampal volume, underscoring its central role in verbal memory impairment in TLE. Associations with the temporal pole and inferior temporal regions suggest additional contributions from extrahippocampal areas. Left hippocampal atrophy exacerbates verbal memory impairment beyond what would be expected from seizure activity alone. The results of this study show that the ability to learn semantically unrelated information and recall unstructured information after a period of delay is particularly compromised in individuals with left hippocampal atrophy. These impairments were strongly associated with reduced left hippocampal volume. In contrast, volumes of the adjacent rhinal cortex were not related to memory performance. These findings underscore the central role of the left hippocampus in supporting verbal memory in temporal lobe epilepsy. This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Given that there are 27 bone stress injury (BSI) severity classification and scoring systems described in the literature, most systems are based solely on imaging, while the literature stresses the importance of considering clinical risk factors for return to running. To propose a modified BSI classification score incorporating clinical factors, bone location, Fredericson and Nattiv magnetic resonance imaging (MRI) grading systems, and bone type to improve prediction of return-to-running times. Cohort study; Level of evidence, 2. A 7-year prospective study of National Collegiate Athletic Association Division I cross-country and track and field athletes was conducted from 2013 to 2020. Participants completed an annual questionnaire about known risk factors for injury or impaired bone health. Information about BSIs and time to return to running was collected at team physician meeti

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function. Understanding age‐related changes of brain function during aging in ASD is crucial to establish best practices for cognitive and health screenings to detect potential accelerated decline in older adults with ASD and to develop interventions that might reduce risk. BSV is an MRI‐based measure that decreases in typical aging and is linked to cognitive decline. In this study, we found that BSV decreases may occur earlier in 40–70‐year old adults with ASD compared to their neurotypical peers, possibly indicating accelerated aging, although additional longitudinal analyses will be required to confirm this. Verbal memory tasks differ in their cognitive demands and may rely on distinct left medial temporal structures. One model holds that verbal delayed recall is hippocampal dependent, whereas verbal paired associate learning relies on adjacent rhinal cortex. We test this by examining the relationship between task performance and regional temporal lobe volumes in individuals with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Retrospective analysis of 99 surgically naïve TLE patients (12 bilateral TLE-HS, 35 left TLE-HS, 28 right TLE-HS, and 24 MRI-negative left TLE) with contemporaneous neuropsychological and T1-weighted MRI data. Delayed recall was operationalized using the Rey Auditory Verbal Learning Test, and arbitrary associative learning with the Paired Associates Learning subtest. Linear regressions assessed associations between memory performance and temporal lobe volumes. We also studied a cohort with nonlesional left TLE to better distinguish the relative impact on verbal memory of left temporal onset seizures versus the structural integrity of the left mesial temporal lobe. Patients with left-sided TLE-HS (unilateral/bilateral) performed significantly worse on both memory measures compared to right TLE-HS and MRI-negative left TLE (p < 0.001). Left hippocampal volume significantly predicted performance on both measures (both p < 0.001), whereas rhinal cortex volumes were not significantly associated with either. Secondary analyses revealed associations between left temporal pole volume and both memory measures, and between inferior temporal gyrus volume and delayed recall. Despite differing cognitive demands, both verbal arbitrary associative learning and delayed recall were primarily linked to left hippocampal volume, underscoring its central role in verbal memory impairment in TLE. Associations with the temporal pole and inferior temporal regions suggest additional contributions from extrahippocampal areas. Left hippocampal atrophy exacerbates verbal memory impairment beyond what would be expected from seizure activity alone. The results of this study show that the ability to learn semantically unrelated information and recall unstructured information after a period of delay is particularly compromised in individuals with left hippocampal atrophy. These impairments were strongly associated with reduced left hippocampal volume. In contrast, volumes of the adjacent rhinal cortex were not related to memory performance. These findings underscore the central role of the left hippocampus in supporting verbal memory in temporal lobe epilepsy. This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Given that there are 27 bone stress injury (BSI) severity classification and scoring systems described in the literature, most systems are based solely on imaging, while the literature stresses the importance of considering clinical risk factors for return to running. To propose a modified BSI classification score incorporating clinical factors, bone location, Fredericson and Nattiv magnetic resonance imaging (MRI) grading systems, and bone type to improve prediction of return-to-running times. Cohort study; Level of evidence, 2. A 7-year prospective study of National Collegiate Athletic Association Division I cross-country and track and field athletes was conducted from 2013 to 2020. Participants completed an annual questionnaire about known risk factors for injury or impaired bone health. Information about BSIs and time to return to running was collected at team physician meeti

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function. Understanding age‐related changes of brain function during aging in ASD is crucial to establish best practices for cognitive and health screenings to detect potential accelerated decline in older adults with ASD and to develop interventions that might reduce risk. BSV is an MRI‐based measure that decreases in typical aging and is linked to cognitive decline. In this study, we found that BSV decreases may occur earlier in 40–70‐year old adults with ASD compared to their neurotypical peers, possibly indicating accelerated aging, although additional longitudinal analyses will be required to confirm this. Verbal memory tasks differ in their cognitive demands and may rely on distinct left medial temporal structures. One model holds that verbal delayed recall is hippocampal dependent, whereas verbal paired associate learning relies on adjacent rhinal cortex. We test this by examining the relationship between task performance and regional temporal lobe volumes in individuals with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS). Retrospective analysis of 99 surgically naïve TLE patients (12 bilateral TLE-HS, 35 left TLE-HS, 28 right TLE-HS, and 24 MRI-negative left TLE) with contemporaneous neuropsychological and T1-weighted MRI data. Delayed recall was operationalized using the Rey Auditory Verbal Learning Test, and arbitrary associative learning with the Paired Associates Learning subtest. Linear regressions assessed associations between memory performance and temporal lobe volumes. We also studied a cohort with nonlesional left TLE to better distinguish the relative impact on verbal memory of left temporal onset seizures versus the structural integrity of the left mesial temporal lobe. Patients with left-sided TLE-HS (unilateral/bilateral) performed significantly worse on both memory measures compared to right TLE-HS and MRI-negative left TLE (p < 0.001). Left hippocampal volume significantly predicted performance on both measures (both p < 0.001), whereas rhinal cortex volumes were not significantly associated with either. Secondary analyses revealed associations between left temporal pole volume and both memory measures, and between inferior temporal gyrus volume and delayed recall. Despite differing cognitive demands, both verbal arbitrary associative learning and delayed recall were primarily linked to left hippocampal volume, underscoring its central role in verbal memory impairment in TLE. Associations with the temporal pole and inferior temporal regions suggest additional contributions from extrahippocampal areas. Left hippocampal atrophy exacerbates verbal memory impairment beyond what would be expected from seizure activity alone. The results of this study show that the ability to learn semantically unrelated information and recall unstructured information after a period of delay is particularly compromised in individuals with left hippocampal atrophy. These impairments were strongly associated with reduced left hippocampal volume. In contrast, volumes of the adjacent rhinal cortex were not related to memory performance. These findings underscore the central role of the left hippocampus in supporting verbal memory in temporal lobe epilepsy. This study investigates a novel femoral ring block technique designed to enhance postoperative analgesia for knee surgeries. Due to the complex innervation of the knee and the significant postoperative pain resulting from surgical interventions, effective regional anesthesia techniques are essential. Traditional methods, such as femoral, genicular nerves, and adductor canal blocks, often require multiple injections and can lead to prolonged procedure times and patient discomfort. This research hypothesizes that a high-volume injection from the midline into the femur would result in a ring-like spread of anesthetic, effectively targeting critical nerves involved in knee innervation. Four lower extremity cadavers with no prior history of knee surgery were included in the study. To enhance visibility, two different solutions (methylene blue-acrylic green dye and saline-radio-opaque substance mixtures) were used to obtain two different colors, as determined by CT and MRI. The ring block was applied to both knees of each cadaver using the same technique and the same solution. The spread was monitored during the injections using real-time ultrasonography. CT and MRI scans were performed after the block applications. Following the imaging procedures, the cadavers were dissected. Results demonstrated that this technique could potentially improve analgesia quality by effectively blocking multiple nerves with a single injection, thereby reducing the number of required injections and shortening block application time. In cadaveric dissections, the superior medial and lateral geniculate nerves, the vastus intermedius and vastus medialis nerves, and the saphenous nerve running along the adductor canal were stained. In conclusion, results demonstrated that six vital nerves for knee analgesia can be blocked with a single needle entry. The new ring block technique showed promising results as a more efficient approach to knee analgesia. Although further clinical researches are needed, this study lays the groundwork for future innovations in regional anesthesia for knee surgery. Given that there are 27 bone stress injury (BSI) severity classification and scoring systems described in the literature, most systems are based solely on imaging, while the literature stresses the importance of considering clinical risk factors for return to running. To propose a modified BSI classification score incorporating clinical factors, bone location, Fredericson and Nattiv magnetic resonance imaging (MRI) grading systems, and bone type to improve prediction of return-to-running times. Cohort study; Level of evidence, 2. A 7-year prospective study of National Collegiate Athletic Association Division I cross-country and track and field athletes was conducted from 2013 to 2020. Participants completed an annual questionnaire about known risk factors for injury or impaired bone health. Information about BSIs and time to return to running was collected at team physician meeti

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

The indole scaffold is common in natural products and bioactive compounds, including anti-cancer and anti-inflammatory medicines. In this work, a series of indole-acrylamide derivatives was synthesized, and their antiproliferative and anti-inflammatory effects were evaluated on COX enzymes and against a panel of cancer cell lines. All the final compounds were characterized via HRMS and (1H & 13C)-NMR. Anticancer and anti-inflammatory activities were evaluated using standard biomedical techniques by SRB, MTS, and COX kit assays. Additionally, the molecular docking analysis was conducted using the AutoDock Vina tool. The results demonstrated that the produced compounds displayed significant inhibitory effects on the COX-2 enzyme, with IC50 values of 128 nM to 1.04 µM. 6a demonstrated significant COX-2 selectivity with an IC50 of 128 nM and an SI of 352, highlighting its preference for COX-2 over COX-1. 6c exhibited potent COX-2 inhibition with an IC50 of 0.215 µM and an SI of 10.6. The assessed compounds exhibited substantial cytotoxic effects on cancer cells, especially against liver cancer cell lines (Huh7, HepG2, Mahlavu, and SNU475), and breast cancer (MCF-7). 6d compound was the most COX-1 selective inhibitor, which observed potent activity against hepatocellular carcinoma, with IC50 values as low as 3.5 µM, and was highly effective against MCF-7. Additionally, COX-2 selective inhibitors, 6a and 6b, exhibited strong antiproliferative effects against both breast cancer (MCF-7) and melanoma (B16F1), with IC50 values ranging from 4.75 to 15.4 µM. Furthermore, the molecular docking of 6a demonstrated a strong affinity for the COX-2 enzyme, with energy scores (S) of -8.392 kcal/mol, comparable to celecoxib's score of -10.96 kcal/mol. The findings suggest a possible correlation between COX-2 inhibition and anticancer efficacy, especially for compounds 6a and 6c, which demonstrate excellent COX-2 selectivity and notable antiproliferative effects, positioning them as prospective candidates for further advancement in cancer treatment. Melasma remains a therapeutically challenging hyperpigmentation disorder due to its high recurrence rate and the limitations of existing topical therapies. Nicotinamide adenine dinucleotide (NAD+) is a fundamental coenzyme critical for mitochondrial bioenergetics, DNA repair, and NAD+-dependent sirtuin-mediated gene regulation. Its systemic decline is implicated in cellular ageing and dysfunction. This study examines a novel procedural intervention, which involves the intradermal delivery of high-dose NAD+ utilizing a microneedling therapy system (MTS). To evaluate the efficacy and safety of a series of microneedling sessions followed by topical sterile NAD+ booster application at three-week intervals for melasma management. A prospective single-centre case series was conducted over 21 weeks involving 36 Korean female patients with mixed-type melasma. Participants received five treatment sessions consisting of MTS immediately followed by NAD+ (Sihler N, Sihler Inc., Korea). The primary outcome measure was the change in Melasma Area and Severity Index (MASI) score from baseline to week 21. Secondary outcomes included blinded photographic evaluation using a 5-point Global Aesthetic Improvement Scale (GAIS) and patient-reported satisfaction measures. All enrolled participants completed the treatment protocol. Analysis revealed a statistically significant reduction in mean MASI score from 16.8 ± 5.2 at baseline to 6.9 ± 3.1 at week 21 (p < 0.001), representing a 59.2% improvement. Independent blinded dermatological assessment rated 83.3% of patients as demonstrating clinical improvement. The procedure demonstrated an excellent safety profile with only transient erythema and oedema observed, resolving spontaneously within 48 hours. The combination of MTS with microneedling-assisted topical application of sterile NAD+ appears to be an effective and well-tolerated intervention for melasma management. The distinct mechanism of action, focused on supporting cellular function, warrants further investigation in randomized controlled designs (e.g. split-face or vehicle-controlled trials). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Ceftobiprole is a new-generation cephalosporin with activity against Staphylococcus aureus, but a comprehensive evaluation of MIC Test Strip (MTS) and disk diffusion (DD) methods using EUCAST and FDA breakpoint is lacking. Using broth microdilution (BMD) as the reference standard, we assessed the performance of MTS and DD for determining ceftobiprole susceptibility among 422 clinical S. aureus isolates. Ceftobiprole retained potent activity, with MIC₅₀/MIC₉₀ of 0.5/1 mg/L and an overall susceptibility rate of 98.8%; methicillin-resistant Staphylococcus aureus (MRSA) showed 97.6% susceptibility. MTS demonstrated high agreement with BMD, achieving 98.8% categorical agreement (CA), 1.2% major error (ME), and zero very major error (VME) under European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, meeting the acceptability limits of ISO 20776-2:2021 and CLSI M52. DD performance was breakpoint-dependent: under EUCAST criteria, the overall CA was 89.6%, with 10.6% ME and 0 VME. The 40.3% of MRSA that fell into the EUCAST-defined Area of Technical Uncertainty (ATU) zone were all shown to be susceptible by the reference BMD method. Under Food and Drug Administration (FDA) breakpoints, the CA rose to 94.1% and ME fell to 1.7%. Consequently, MTS offers a reliable routine option; DD is suitable for routine testing under FDA breakpoints, while for EUCAST users, MRSA isolates in the ATU zone should be confirmed by BMD or MTS. VME was not determined under FDA breakpoints due to the absence of resistant isolates. Ceftobiprole offers a β-lactam option for Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA); however, its susceptibility testing remains insufficiently examined across both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA) interpretive criteria. We systematically compared MIC Test Strip (MTS) and disk diffusion (DD) with broth microdilution (BMD), demonstrating breakpoint-specific performance for methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA and providing practical recommendations that allow laboratories to report accurate results regardless of the guidelines they follow. Human rhinovirus (HRV) is a highly widespread pathogen, the most frequent cause of the common cold, and often associated with asthma exacerbation. To date, attempts to develop direct-acting antivirals (DAAs) have proved unsuccessful, also due to their tendency to select resistant variants when challenged with HRV quasispecies. 27-hydroxycholesterol (27OHC), a cholesterol-derived host-targeting antiviral (HTA), inhibits HRV replication and is less prone to selecting resistant variants than the DAAs pleconaril and rupintrivir. In the present study, we developed and evaluated a lipid nanoparticle (LNP)-based formulation for the nasal delivery of 27OHC. The antiviral efficacy of 27OHC-loaded LNPs was assessed on HeLa cells by focus reduction assays and yield reduction assays. The effect on cell viability and the cytotoxicity were determined via MTS and LDH assays to calculate the 50% cytotoxic concentration (CC50). Efficacy and biocompatibility of 27OHC were further validated in a physiologically relevant 3D model of reconstituted human nasal epithelia derived from healthy donors. Cellular uptake and internalization kinetics of LNPs were assessed on HeLa cells with the use of fluorochrome-tagged LNPs and i

Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in the neovasculature of some pancreatic ductal adenocarcinoma (PDAC). PET/CT can detect this expression and has now become an essential tool in this context. However, this antigen can also be expressed by other neoplasms. While this may create diagnostic uncertainty, it could also open therapeutic opportunities. Here we describe a case in which a PET/CT performed to restage a patient with prostate adenocarcinoma experiencing biochemical recurrence revealed the coexistence of a PDAC. A literature review aimed to summarize the bibliographic evidence on the use of this technique in this setting, which is relatively uncommon. Prostate-specific membrane antigen can be overexpressed in PDACs. This finding may offer potential for theranostic applications. Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation. Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET-guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET-guided intensification of postprostatectomy SRT. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET-guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence-free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale. Statistical significance was set at two-sided P<0.05. Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET-guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33-1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. PSMA PET-guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. https://www.crd.york.ac.uk/prospero/, identifier CRD420261277044. Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening variant of antiphospholipid syndrome (APS), characterized by rapid-onset thrombosis affecting multiple organs in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid syndrome is often triggered by an underlying condition, such as infection or malignancy. Early diagnosis and initiation of combination therapy are crucial, given the associated high morbidity and mortality. A 74-year-old woman presented with progressive dyspnoea and acute right-hand ischaemia. Imaging and laboratory work-up revealed widespread arterial and venous thromboses, including pulmonary embolism, brachial artery embolism, carotid artery involvement, and popliteal vein thrombosis. Laboratory tests showed positive lupus anticoagulant, raising suspicion for CAPS. She was treated with intravenous unfractionated heparin, high-dose corticosteroids, and intravenous immunoglobulins. A PET-CT revealed suspected pulmonary adenocarcinoma, which was confirmed via lymph node biopsy. Following initial clinical improvement and discharge on warfarin, she was readmitted with critical limb ischaemia and later on she suffered an ischaemic stroke. Despite endovascular interventions, her condition deteriorated. Given her poor prognosis and ineligibility for oncologic therapy, comfort care was initiated. The patient passed away a few days later. This case highlights the diagnostic and therapeutic challenges of probable CAPS in the context of occult malignancy. Catastrophic antiphospholipid syndrome should be considered in patients presenting with simultaneous arterial and venous thrombotic events. Underlying malignancy may contribute to treatment resistance and worsen prognosis, emphasizing the need for early recognition and multidisciplinary management. Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathw

Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in the neovasculature of some pancreatic ductal adenocarcinoma (PDAC). PET/CT can detect this expression and has now become an essential tool in this context. However, this antigen can also be expressed by other neoplasms. While this may create diagnostic uncertainty, it could also open therapeutic opportunities. Here we describe a case in which a PET/CT performed to restage a patient with prostate adenocarcinoma experiencing biochemical recurrence revealed the coexistence of a PDAC. A literature review aimed to summarize the bibliographic evidence on the use of this technique in this setting, which is relatively uncommon. Prostate-specific membrane antigen can be overexpressed in PDACs. This finding may offer potential for theranostic applications. Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation. Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET-guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET-guided intensification of postprostatectomy SRT. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET-guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence-free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale. Statistical significance was set at two-sided P<0.05. Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET-guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33-1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. PSMA PET-guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. https://www.crd.york.ac.uk/prospero/, identifier CRD420261277044. Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening variant of antiphospholipid syndrome (APS), characterized by rapid-onset thrombosis affecting multiple organs in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid syndrome is often triggered by an underlying condition, such as infection or malignancy. Early diagnosis and initiation of combination therapy are crucial, given the associated high morbidity and mortality. A 74-year-old woman presented with progressive dyspnoea and acute right-hand ischaemia. Imaging and laboratory work-up revealed widespread arterial and venous thromboses, including pulmonary embolism, brachial artery embolism, carotid artery involvement, and popliteal vein thrombosis. Laboratory tests showed positive lupus anticoagulant, raising suspicion for CAPS. She was treated with intravenous unfractionated heparin, high-dose corticosteroids, and intravenous immunoglobulins. A PET-CT revealed suspected pulmonary adenocarcinoma, which was confirmed via lymph node biopsy. Following initial clinical improvement and discharge on warfarin, she was readmitted with critical limb ischaemia and later on she suffered an ischaemic stroke. Despite endovascular interventions, her condition deteriorated. Given her poor prognosis and ineligibility for oncologic therapy, comfort care was initiated. The patient passed away a few days later. This case highlights the diagnostic and therapeutic challenges of probable CAPS in the context of occult malignancy. Catastrophic antiphospholipid syndrome should be considered in patients presenting with simultaneous arterial and venous thrombotic events. Underlying malignancy may contribute to treatment resistance and worsen prognosis, emphasizing the need for early recognition and multidisciplinary management. Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathw

Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in the neovasculature of some pancreatic ductal adenocarcinoma (PDAC). PET/CT can detect this expression and has now become an essential tool in this context. However, this antigen can also be expressed by other neoplasms. While this may create diagnostic uncertainty, it could also open therapeutic opportunities. Here we describe a case in which a PET/CT performed to restage a patient with prostate adenocarcinoma experiencing biochemical recurrence revealed the coexistence of a PDAC. A literature review aimed to summarize the bibliographic evidence on the use of this technique in this setting, which is relatively uncommon. Prostate-specific membrane antigen can be overexpressed in PDACs. This finding may offer potential for theranostic applications. Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation. Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET-guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET-guided intensification of postprostatectomy SRT. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET-guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence-free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale. Statistical significance was set at two-sided P<0.05. Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET-guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33-1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. PSMA PET-guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. https://www.crd.york.ac.uk/prospero/, identifier CRD420261277044. Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening variant of antiphospholipid syndrome (APS), characterized by rapid-onset thrombosis affecting multiple organs in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid syndrome is often triggered by an underlying condition, such as infection or malignancy. Early diagnosis and initiation of combination therapy are crucial, given the associated high morbidity and mortality. A 74-year-old woman presented with progressive dyspnoea and acute right-hand ischaemia. Imaging and laboratory work-up revealed widespread arterial and venous thromboses, including pulmonary embolism, brachial artery embolism, carotid artery involvement, and popliteal vein thrombosis. Laboratory tests showed positive lupus anticoagulant, raising suspicion for CAPS. She was treated with intravenous unfractionated heparin, high-dose corticosteroids, and intravenous immunoglobulins. A PET-CT revealed suspected pulmonary adenocarcinoma, which was confirmed via lymph node biopsy. Following initial clinical improvement and discharge on warfarin, she was readmitted with critical limb ischaemia and later on she suffered an ischaemic stroke. Despite endovascular interventions, her condition deteriorated. Given her poor prognosis and ineligibility for oncologic therapy, comfort care was initiated. The patient passed away a few days later. This case highlights the diagnostic and therapeutic challenges of probable CAPS in the context of occult malignancy. Catastrophic antiphospholipid syndrome should be considered in patients presenting with simultaneous arterial and venous thrombotic events. Underlying malignancy may contribute to treatment resistance and worsen prognosis, emphasizing the need for early recognition and multidisciplinary management. Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathw

Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in the neovasculature of some pancreatic ductal adenocarcinoma (PDAC). PET/CT can detect this expression and has now become an essential tool in this context. However, this antigen can also be expressed by other neoplasms. While this may create diagnostic uncertainty, it could also open therapeutic opportunities. Here we describe a case in which a PET/CT performed to restage a patient with prostate adenocarcinoma experiencing biochemical recurrence revealed the coexistence of a PDAC. A literature review aimed to summarize the bibliographic evidence on the use of this technique in this setting, which is relatively uncommon. Prostate-specific membrane antigen can be overexpressed in PDACs. This finding may offer potential for theranostic applications. Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation. Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET-guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET-guided intensification of postprostatectomy SRT. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET-guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence-free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale. Statistical significance was set at two-sided P<0.05. Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET-guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33-1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. PSMA PET-guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. https://www.crd.york.ac.uk/prospero/, identifier CRD420261277044. Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening variant of antiphospholipid syndrome (APS), characterized by rapid-onset thrombosis affecting multiple organs in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid syndrome is often triggered by an underlying condition, such as infection or malignancy. Early diagnosis and initiation of combination therapy are crucial, given the associated high morbidity and mortality. A 74-year-old woman presented with progressive dyspnoea and acute right-hand ischaemia. Imaging and laboratory work-up revealed widespread arterial and venous thromboses, including pulmonary embolism, brachial artery embolism, carotid artery involvement, and popliteal vein thrombosis. Laboratory tests showed positive lupus anticoagulant, raising suspicion for CAPS. She was treated with intravenous unfractionated heparin, high-dose corticosteroids, and intravenous immunoglobulins. A PET-CT revealed suspected pulmonary adenocarcinoma, which was confirmed via lymph node biopsy. Following initial clinical improvement and discharge on warfarin, she was readmitted with critical limb ischaemia and later on she suffered an ischaemic stroke. Despite endovascular interventions, her condition deteriorated. Given her poor prognosis and ineligibility for oncologic therapy, comfort care was initiated. The patient passed away a few days later. This case highlights the diagnostic and therapeutic challenges of probable CAPS in the context of occult malignancy. Catastrophic antiphospholipid syndrome should be considered in patients presenting with simultaneous arterial and venous thrombotic events. Underlying malignancy may contribute to treatment resistance and worsen prognosis, emphasizing the need for early recognition and multidisciplinary management. Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathw

Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in the neovasculature of some pancreatic ductal adenocarcinoma (PDAC). PET/CT can detect this expression and has now become an essential tool in this context. However, this antigen can also be expressed by other neoplasms. While this may create diagnostic uncertainty, it could also open therapeutic opportunities. Here we describe a case in which a PET/CT performed to restage a patient with prostate adenocarcinoma experiencing biochemical recurrence revealed the coexistence of a PDAC. A literature review aimed to summarize the bibliographic evidence on the use of this technique in this setting, which is relatively uncommon. Prostate-specific membrane antigen can be overexpressed in PDACs. This finding may offer potential for theranostic applications. Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation. Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET-guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET-guided intensification of postprostatectomy SRT. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET-guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence-free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale. Statistical significance was set at two-sided P<0.05. Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET-guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33-1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. PSMA PET-guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. https://www.crd.york.ac.uk/prospero/, identifier CRD420261277044. Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening variant of antiphospholipid syndrome (APS), characterized by rapid-onset thrombosis affecting multiple organs in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid syndrome is often triggered by an underlying condition, such as infection or malignancy. Early diagnosis and initiation of combination therapy are crucial, given the associated high morbidity and mortality. A 74-year-old woman presented with progressive dyspnoea and acute right-hand ischaemia. Imaging and laboratory work-up revealed widespread arterial and venous thromboses, including pulmonary embolism, brachial artery embolism, carotid artery involvement, and popliteal vein thrombosis. Laboratory tests showed positive lupus anticoagulant, raising suspicion for CAPS. She was treated with intravenous unfractionated heparin, high-dose corticosteroids, and intravenous immunoglobulins. A PET-CT revealed suspected pulmonary adenocarcinoma, which was confirmed via lymph node biopsy. Following initial clinical improvement and discharge on warfarin, she was readmitted with critical limb ischaemia and later on she suffered an ischaemic stroke. Despite endovascular interventions, her condition deteriorated. Given her poor prognosis and ineligibility for oncologic therapy, comfort care was initiated. The patient passed away a few days later. This case highlights the diagnostic and therapeutic challenges of probable CAPS in the context of occult malignancy. Catastrophic antiphospholipid syndrome should be considered in patients presenting with simultaneous arterial and venous thrombotic events. Underlying malignancy may contribute to treatment resistance and worsen prognosis, emphasizing the need for early recognition and multidisciplinary management. Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathw

Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in the neovasculature of some pancreatic ductal adenocarcinoma (PDAC). PET/CT can detect this expression and has now become an essential tool in this context. However, this antigen can also be expressed by other neoplasms. While this may create diagnostic uncertainty, it could also open therapeutic opportunities. Here we describe a case in which a PET/CT performed to restage a patient with prostate adenocarcinoma experiencing biochemical recurrence revealed the coexistence of a PDAC. A literature review aimed to summarize the bibliographic evidence on the use of this technique in this setting, which is relatively uncommon. Prostate-specific membrane antigen can be overexpressed in PDACs. This finding may offer potential for theranostic applications. Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation. Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET-guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET-guided intensification of postprostatectomy SRT. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET-guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence-free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale. Statistical significance was set at two-sided P<0.05. Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET-guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33-1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. PSMA PET-guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. https://www.crd.york.ac.uk/prospero/, identifier CRD420261277044. Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening variant of antiphospholipid syndrome (APS), characterized by rapid-onset thrombosis affecting multiple organs in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid syndrome is often triggered by an underlying condition, such as infection or malignancy. Early diagnosis and initiation of combination therapy are crucial, given the associated high morbidity and mortality. A 74-year-old woman presented with progressive dyspnoea and acute right-hand ischaemia. Imaging and laboratory work-up revealed widespread arterial and venous thromboses, including pulmonary embolism, brachial artery embolism, carotid artery involvement, and popliteal vein thrombosis. Laboratory tests showed positive lupus anticoagulant, raising suspicion for CAPS. She was treated with intravenous unfractionated heparin, high-dose corticosteroids, and intravenous immunoglobulins. A PET-CT revealed suspected pulmonary adenocarcinoma, which was confirmed via lymph node biopsy. Following initial clinical improvement and discharge on warfarin, she was readmitted with critical limb ischaemia and later on she suffered an ischaemic stroke. Despite endovascular interventions, her condition deteriorated. Given her poor prognosis and ineligibility for oncologic therapy, comfort care was initiated. The patient passed away a few days later. This case highlights the diagnostic and therapeutic challenges of probable CAPS in the context of occult malignancy. Catastrophic antiphospholipid syndrome should be considered in patients presenting with simultaneous arterial and venous thrombotic events. Underlying malignancy may contribute to treatment resistance and worsen prognosis, emphasizing the need for early recognition and multidisciplinary management. Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathw

Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in the neovasculature of some pancreatic ductal adenocarcinoma (PDAC). PET/CT can detect this expression and has now become an essential tool in this context. However, this antigen can also be expressed by other neoplasms. While this may create diagnostic uncertainty, it could also open therapeutic opportunities. Here we describe a case in which a PET/CT performed to restage a patient with prostate adenocarcinoma experiencing biochemical recurrence revealed the coexistence of a PDAC. A literature review aimed to summarize the bibliographic evidence on the use of this technique in this setting, which is relatively uncommon. Prostate-specific membrane antigen can be overexpressed in PDACs. This finding may offer potential for theranostic applications. Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation. Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET-guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET-guided intensification of postprostatectomy SRT. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET-guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence-free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale. Statistical significance was set at two-sided P<0.05. Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET-guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33-1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. PSMA PET-guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. https://www.crd.york.ac.uk/prospero/, identifier CRD420261277044. Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening variant of antiphospholipid syndrome (APS), characterized by rapid-onset thrombosis affecting multiple organs in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid syndrome is often triggered by an underlying condition, such as infection or malignancy. Early diagnosis and initiation of combination therapy are crucial, given the associated high morbidity and mortality. A 74-year-old woman presented with progressive dyspnoea and acute right-hand ischaemia. Imaging and laboratory work-up revealed widespread arterial and venous thromboses, including pulmonary embolism, brachial artery embolism, carotid artery involvement, and popliteal vein thrombosis. Laboratory tests showed positive lupus anticoagulant, raising suspicion for CAPS. She was treated with intravenous unfractionated heparin, high-dose corticosteroids, and intravenous immunoglobulins. A PET-CT revealed suspected pulmonary adenocarcinoma, which was confirmed via lymph node biopsy. Following initial clinical improvement and discharge on warfarin, she was readmitted with critical limb ischaemia and later on she suffered an ischaemic stroke. Despite endovascular interventions, her condition deteriorated. Given her poor prognosis and ineligibility for oncologic therapy, comfort care was initiated. The patient passed away a few days later. This case highlights the diagnostic and therapeutic challenges of probable CAPS in the context of occult malignancy. Catastrophic antiphospholipid syndrome should be considered in patients presenting with simultaneous arterial and venous thrombotic events. Underlying malignancy may contribute to treatment resistance and worsen prognosis, emphasizing the need for early recognition and multidisciplinary management. Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathw

Malignant lymphoma in the breast is rare, with primary breast lymphoma and secondary breast lymphoma being the two subtypes. Primary breast lymphoma presents as a fast-growing, painless, palpable mass and is less frequent due to limited lymphoid tissue in the breast. Primary breast double-hit lymphoma is a very rare, highly aggressive malignancy that presents a great challenge regarding proper diagnosis and optimal treatment. Our case involved high-grade B-cell lymphoma with MYC and BCL2 rearrangement (double hit), treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin chemotherapy, resulting in complete resolution. Prostate specific membrane antigen (PSMA) is a type II transmembrane protein overexpressed in the neovasculature of some pancreatic ductal adenocarcinoma (PDAC). PET/CT can detect this expression and has now become an essential tool in this context. However, this antigen can also be expressed by other neoplasms. While this may create diagnostic uncertainty, it could also open therapeutic opportunities. Here we describe a case in which a PET/CT performed to restage a patient with prostate adenocarcinoma experiencing biochemical recurrence revealed the coexistence of a PDAC. A literature review aimed to summarize the bibliographic evidence on the use of this technique in this setting, which is relatively uncommon. Prostate-specific membrane antigen can be overexpressed in PDACs. This finding may offer potential for theranostic applications. Although histopathological evaluation of myocardium is essential for detecting both acute cellular rejection (ACR) and antibody-mediated rejection (AMR) following heart transplantation, indeterminate results and complication risks associated with repeated endomyocardial biopsies remain serious problems. We investigated the clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to detect rejection. This retrospective single-center study reviewed the clinical data of heart-transplant recipients at our institution between 2008 and 2022. Patients who underwent 18F-FDG PET/CT scans post-transplant were enrolled. Scans were performed following a high-fat, low-carbohydrate diet initiated 24 hours before imaging and an 18-hour fasting period. FDG uptake was represented as cardiac metabolic volume (CMV), maximum standard uptake value (SUVmax), and total lesion glycolysis (TLG). During the study period, 132 18F-FDG PET/CT scans in 40 heart-transplant recipients were identified. Age at transplant was 53 [43-62] years old, and 29 patients (73%) were male. We found 10 scans at the time of significant ACR. No patients experienced AMR. At the time of ACR, CMV (88.2 [22.5-275.8] vs 0.0 [0.0-7.3] ml, p < 0.001), SUVmax (9.21 [6.87-16.0] vs 2.98 [2.49-4.48], p < 0.001) and TLG (365.3 [78.3-1,908.7] vs 0.0 [0.0-25.8] g, p < 0.001) were significantly higher compared to those without rejection. From baseline to the time of ACR, significant increases of CMV, SUVmax, and TLG (p < 0.001 for all) were also found. FDG uptake was significantly elevated at the time of ACR. 18F-FDG PET/CT may represent a promising non-invasive diagnostic adjunct for detecting ACR following heart transplantation. Prostate-specific membrane antigen (PSMA) PET is used to guide postprostatectomy salvage radiotherapy (SRT) and enable intensification through dose escalation and target modification. The oncologic benefit and safety profile of PSMA PET-guided intensification remain uncertain. We aimed to synthesize comparative and single-arm evidence on oncologic outcomes and toxicity of PSMA PET-guided intensification of postprostatectomy SRT. We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Embase and Cochrane Library were searched from inception to 26 December 2025. Comparative and single-arm studies evaluating PSMA PET-guided intensification of postprostatectomy SRT were included. We included clinical studies using PSMA PET/CT or PET/MRI to guide radiotherapy intensification and excluded preclinical studies and non-original reports. Primary outcomes were failure-free survival (FFS) and biochemical recurrence-free survival (bRFS). Secondary outcomes included metastasis- and survival-related endpoints, treatment escalation, and toxicity. Meta-analysis was conducted only when sufficient comparative data were available. Hazard ratios were pooled in RevMan 5.4.1 using fixed- or random-effects models according to heterogeneity. Risk of bias was assessed with the Newcastle-Ottawa Scale. Statistical significance was set at two-sided P<0.05. Fifteen studies met inclusion criteria, including five comparative and ten single-arm studies. Two studies reported FFS-type endpoints; because only two studies were available and endpoint definitions differed substantially, these findings were summarized descriptively. Four comparative studies involving 692 patients contributed to bRFS meta-analysis. PSMA PET-guided SRT showed numerically improved bRFS versus standard SRT, but the difference was not statistically significant (pooled HR 0.61, 95% CI 0.33-1.13; P = 0.12; I²=55%). Other secondary oncologic outcomes were variably reported with limited events and were synthesized descriptively. Severe genitourinary or gastrointestinal toxicity was uncommon, and some studies suggested delayed treatment escalation. PSMA PET-guided intensification of postprostatectomy SRT may improve biochemical control without an increase in severe toxicity; however, a statistically significant bRFS benefit was not demonstrated and evidence for other oncologic outcomes remains limited. https://www.crd.york.ac.uk/prospero/, identifier CRD420261277044. Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening variant of antiphospholipid syndrome (APS), characterized by rapid-onset thrombosis affecting multiple organs in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid syndrome is often triggered by an underlying condition, such as infection or malignancy. Early diagnosis and initiation of combination therapy are crucial, given the associated high morbidity and mortality. A 74-year-old woman presented with progressive dyspnoea and acute right-hand ischaemia. Imaging and laboratory work-up revealed widespread arterial and venous thromboses, including pulmonary embolism, brachial artery embolism, carotid artery involvement, and popliteal vein thrombosis. Laboratory tests showed positive lupus anticoagulant, raising suspicion for CAPS. She was treated with intravenous unfractionated heparin, high-dose corticosteroids, and intravenous immunoglobulins. A PET-CT revealed suspected pulmonary adenocarcinoma, which was confirmed via lymph node biopsy. Following initial clinical improvement and discharge on warfarin, she was readmitted with critical limb ischaemia and later on she suffered an ischaemic stroke. Despite endovascular interventions, her condition deteriorated. Given her poor prognosis and ineligibility for oncologic therapy, comfort care was initiated. The patient passed away a few days later. This case highlights the diagnostic and therapeutic challenges of probable CAPS in the context of occult malignancy. Catastrophic antiphospholipid syndrome should be considered in patients presenting with simultaneous arterial and venous thrombotic events. Underlying malignancy may contribute to treatment resistance and worsen prognosis, emphasizing the need for early recognition and multidisciplinary management. Metastasis-directed stereotactic body radiotherapy (MD-SBRT) has shown promise in retrospective and phase II studies for oligometastatic hormone-sensitive prostate cancer. However, prospective randomized phase III data-particularly in newly diagnosed cases and in combination with androgen deprivation therapy and next-generation androgen receptor pathw

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Hip fractures are among the most devastating complications of osteoporosis, yet determinants of the Fracture Risk Assessment Tool (FRAX)-estimated 10-year hip fracture probability (FRAX-Hip) in rheumatoid arthritis (RA) remain incompletely defined. The incremental value of RA disease activity and complete blood count (CBC)-derived inflammatory indices beyond traditional FRAX clinical risk factors is uncertain. To identify determinants of 10-year FRAX-Hip risk in RA and to compare the predictive performance and incremental value of RA disease activity indices and CBC-derived inflammatory markers. In a cross-sectional cohort of 248 RA patients undergoing dual-energy X-ray absorptiometry, we calculated femoral neck bone mineral density (BMD)-adjusted FRAX-Hip and defined high risk as FRAX-Hip ≥3%. Determinants were assessed using Firth penalized logistic regression and multivariable linear regression, and incremental value was evaluated using changes in area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). High FRAX-Hip risk was mainly driven by older age, female sex, lower body mass index, glucocorticoid exposure, and lower femoral neck BMD. Among disease activity measures, the Simplified Disease Activity Index (SDAI) provided the largest-yet modest-incremental improvement over a base clinical model (ΔAUC = 0.013; NRI = 0.903; IDI = 0.075). In contrast, CBC-derived inflammatory indices showed poor discrimination (AUC 0.46-0.62) and negligible incremental value. The clinical model explained >93% of the variance in log-transformed FRAX-Hip. Traditional FRAX clinical factors dominate FRAX-Hip risk estimation in RA. SDAI adds only modest incremental value, whereas CBC-derived indices do not improve risk stratification. FRAX with BMD remains a robust tool for identifying high-risk patients, underscoring the importance of optimizing age-, glucocorticoid-, and bone density-related risk factors while maintaining tight RA disease control. Over the past few decades, X-ray computed tomography (CT) has been introduced as one of the main cross-sectional imaging methods in a wide range of clinical applications in diagnostic radiology, oncology, and multimodality molecular imaging. Despite the acknowledged value of this imaging method, in some cases, the quality of CT images is affected by the presence of metallic implants. The presence of metal objects such as dental fillings, hip or knee prostheses, pacemakers, war shrapnel, and spinal cages cause and exacerbate image artifacts. These types of artifacts appear in the image as black and white lines that obscure the structures and tissues surrounding the metal implant and destroy the diagnostic value of CT images. These artifacts also affect the accuracy of radiotherapy treatment planning, which relies on CT images to characterize electron density and estimate the relative stopping power of particles. Therefore, to solve this problem, over the past 4 decades, algorithms called Metal Artifact Reduction (MAR) have been proposed. The objective of this study was to assess the five MAR algorithms using simulation and clinical studies. The algorithms include linear interpolation (LI-MAR) of degraded data in sinograms, normalization metal artifact reduction (NMAR), metal removal method (MDT), metal artifact reducer for orthopedic implants (OMAR), and a method based on iteration-based algorithms (MAP). Clinical images in different body regions, with different dimensions and types of metal implants, have been studied to evaluate the performance of MAR algorithms. To quantitatively assess the quality of images modified with MAR algorithms, the normalized root mean square error (NRMSE) criterion has been calculated and evaluated. The results of the algorithm evaluation showed that the NMAR algorithm was more efficient than other algorithms in reducing metal artifacts in most cases. Also, the algorithm processing time parameter demonstrated the clinical value of the NMAR algorithm. With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors. We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice. This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of "positive regulation" of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum. Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy. Foreign body aspiration (FBA) in adults is rare and often overlooked, presenting with nonspecific pulmonary symptoms that may mimic recurrent infections or malignancy. Delay in diagnosis can lead to prolonged morbidity and mismanagement. We report a 55-year-old woman with a 2-month history of productive cough, intermittent hemoptysis, dyspnea, pleuritic chest pain, and recurrent pneumonia unresponsive to multiple courses of antibiotics and corticosteroids. Chest X-ray revealed right middle-lobe collapse, while computed tomography demonstrated a linear radiopaque lesion in the right middle-lobe bronchus. Flexible bronchoscopy confirmed complete bronchial obstruction by purulent debris concealing a sharp chicken bone fragment, which was retrieved successfully. The patient showed rapid clinical improvement following removal. This case underscores the importance of considering FBA in the differential diagnosis of persistent atelectasis or treatment-resistant pneumonia in adults, even in the absence of aspiration history or risk factors. Diagnostic bronchoscopy remains the gold standard, enabling both definitive diagnosis and therapeutic intervention, thereby preventing misdiagnosis as neoplasm and avoiding unnecessary procedures. Liver fibrosis is the key determinant of prognosis in metabolic dysfunction-associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3668 U S. adults participating in NHANES 2017-2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clini

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways. There is conflicting evidence for the optimal method of analgesia following posterior spinal fusion for adolescent idiopathic scoliosis. The primary objective of this study is to test which method of postoperative analgesia (continuous epidural, spinal opioids, or patient-controlled analgesia) is associated with reduced opioid requirements, pain scores, complications, and length of stay. This is a retrospective, multicenter study of the Shriners Children's International Pediatric Spine Database. Patients ages 13 to 19 years who had posterior spinal fusion with segmental spinal instrumentation for adolescent idiopathic scoliosis between January 01, 2011, and November 5, 2021, were eligible. Patients were divided into 3 cohorts based on the primary method of postoperative analgesia: continuous epidural (EPI), spinal opioid (SPI), or patient-controlled analgesia (PCA). We compared total parenteral and oral opioid usage, verbal numeric pain scores, complications, and the length of stay. A total of 2371 patients from 13 hospitals were included in the study. Total parenteral and oral opioid usage in the spinal and epidural groups was significantly lower compared with the patient-controlled analgesia group [OME/kg: SPI 1.7 (95% CI: 1.1-2.5) vs. EPI 1.9 (95% CI: 1.1-3.2) vs. PCA 4.1 (95% CI: 3.4-4.8): P<0.002]. There were no clinically significant differences in mean daily pain scores, complications, or length of stay. Spinal opioid and continuous epidural analgesia decrease parenteral and oral opioid requirements compared with patient-controlled analgesia. The increased opioid usage in the patient-controlled analgesia group does not lead to clinically significant differences in pain scores, complications or length of stay. We conclude that all 3 methods of analgesia provide safe and effective pain relief. This study reinforces the need for collaboration between pediatric orthopaedic surgeons and anesthesiologists to effectively manage postoperative pain following posterior spinal fusion for adolescent idiopathic scoliosis. Level III-therapeutic study. Osteosarcoma, the most aggressive primary malignant bone tumor, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5-year overall survival (OS) is <30% for metastatic/recurrent cases. Plagued by genomic heterogeneity, immunosuppressive TME, and low immunogenicity, emerging immunotherapies lack robust large-scale clinical validation. We systematically analyzed 864 interventional osteosarcoma trials from Trialtrove (as of September 2025). Results showed trial numbers peaked at 54 in 2021, with 77.3% past (completed/terminated) and over 94% in phase I/II (only 3.6% phase III-IV). Geographically, the U.S. dominated (60.9%, focusing on immunotherapy/targeted therapy), while low- and middle-income countries (LMICs) accounted for <2%

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways. There is conflicting evidence for the optimal method of analgesia following posterior spinal fusion for adolescent idiopathic scoliosis. The primary objective of this study is to test which method of postoperative analgesia (continuous epidural, spinal opioids, or patient-controlled analgesia) is associated with reduced opioid requirements, pain scores, complications, and length of stay. This is a retrospective, multicenter study of the Shriners Children's International Pediatric Spine Database. Patients ages 13 to 19 years who had posterior spinal fusion with segmental spinal instrumentation for adolescent idiopathic scoliosis between January 01, 2011, and November 5, 2021, were eligible. Patients were divided into 3 cohorts based on the primary method of postoperative analgesia: continuous epidural (EPI), spinal opioid (SPI), or patient-controlled analgesia (PCA). We compared total parenteral and oral opioid usage, verbal numeric pain scores, complications, and the length of stay. A total of 2371 patients from 13 hospitals were included in the study. Total parenteral and oral opioid usage in the spinal and epidural groups was significantly lower compared with the patient-controlled analgesia group [OME/kg: SPI 1.7 (95% CI: 1.1-2.5) vs. EPI 1.9 (95% CI: 1.1-3.2) vs. PCA 4.1 (95% CI: 3.4-4.8): P<0.002]. There were no clinically significant differences in mean daily pain scores, complications, or length of stay. Spinal opioid and continuous epidural analgesia decrease parenteral and oral opioid requirements compared with patient-controlled analgesia. The increased opioid usage in the patient-controlled analgesia group does not lead to clinically significant differences in pain scores, complications or length of stay. We conclude that all 3 methods of analgesia provide safe and effective pain relief. This study reinforces the need for collaboration between pediatric orthopaedic surgeons and anesthesiologists to effectively manage postoperative pain following posterior spinal fusion for adolescent idiopathic scoliosis. Level III-therapeutic study. Osteosarcoma, the most aggressive primary malignant bone tumor, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5-year overall survival (OS) is <30% for metastatic/recurrent cases. Plagued by genomic heterogeneity, immunosuppressive TME, and low immunogenicity, emerging immunotherapies lack robust large-scale clinical validation. We systematically analyzed 864 interventional osteosarcoma trials from Trialtrove (as of September 2025). Results showed trial numbers peaked at 54 in 2021, with 77.3% past (completed/terminated) and over 94% in phase I/II (only 3.6% phase III-IV). Geographically, the U.S. dominated (60.9%, focusing on immunotherapy/targeted therapy), while low- and middle-income countries (LMICs) accounted for <2%

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways. There is conflicting evidence for the optimal method of analgesia following posterior spinal fusion for adolescent idiopathic scoliosis. The primary objective of this study is to test which method of postoperative analgesia (continuous epidural, spinal opioids, or patient-controlled analgesia) is associated with reduced opioid requirements, pain scores, complications, and length of stay. This is a retrospective, multicenter study of the Shriners Children's International Pediatric Spine Database. Patients ages 13 to 19 years who had posterior spinal fusion with segmental spinal instrumentation for adolescent idiopathic scoliosis between January 01, 2011, and November 5, 2021, were eligible. Patients were divided into 3 cohorts based on the primary method of postoperative analgesia: continuous epidural (EPI), spinal opioid (SPI), or patient-controlled analgesia (PCA). We compared total parenteral and oral opioid usage, verbal numeric pain scores, complications, and the length of stay. A total of 2371 patients from 13 hospitals were included in the study. Total parenteral and oral opioid usage in the spinal and epidural groups was significantly lower compared with the patient-controlled analgesia group [OME/kg: SPI 1.7 (95% CI: 1.1-2.5) vs. EPI 1.9 (95% CI: 1.1-3.2) vs. PCA 4.1 (95% CI: 3.4-4.8): P<0.002]. There were no clinically significant differences in mean daily pain scores, complications, or length of stay. Spinal opioid and continuous epidural analgesia decrease parenteral and oral opioid requirements compared with patient-controlled analgesia. The increased opioid usage in the patient-controlled analgesia group does not lead to clinically significant differences in pain scores, complications or length of stay. We conclude that all 3 methods of analgesia provide safe and effective pain relief. This study reinforces the need for collaboration between pediatric orthopaedic surgeons and anesthesiologists to effectively manage postoperative pain following posterior spinal fusion for adolescent idiopathic scoliosis. Level III-therapeutic study. Osteosarcoma, the most aggressive primary malignant bone tumor, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5-year overall survival (OS) is <30% for metastatic/recurrent cases. Plagued by genomic heterogeneity, immunosuppressive TME, and low immunogenicity, emerging immunotherapies lack robust large-scale clinical validation. We systematically analyzed 864 interventional osteosarcoma trials from Trialtrove (as of September 2025). Results showed trial numbers peaked at 54 in 2021, with 77.3% past (completed/terminated) and over 94% in phase I/II (only 3.6% phase III-IV). Geographically, the U.S. dominated (60.9%, focusing on immunotherapy/targeted therapy), while low- and middle-income countries (LMICs) accounted for <2%

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways. There is conflicting evidence for the optimal method of analgesia following posterior spinal fusion for adolescent idiopathic scoliosis. The primary objective of this study is to test which method of postoperative analgesia (continuous epidural, spinal opioids, or patient-controlled analgesia) is associated with reduced opioid requirements, pain scores, complications, and length of stay. This is a retrospective, multicenter study of the Shriners Children's International Pediatric Spine Database. Patients ages 13 to 19 years who had posterior spinal fusion with segmental spinal instrumentation for adolescent idiopathic scoliosis between January 01, 2011, and November 5, 2021, were eligible. Patients were divided into 3 cohorts based on the primary method of postoperative analgesia: continuous epidural (EPI), spinal opioid (SPI), or patient-controlled analgesia (PCA). We compared total parenteral and oral opioid usage, verbal numeric pain scores, complications, and the length of stay. A total of 2371 patients from 13 hospitals were included in the study. Total parenteral and oral opioid usage in the spinal and epidural groups was significantly lower compared with the patient-controlled analgesia group [OME/kg: SPI 1.7 (95% CI: 1.1-2.5) vs. EPI 1.9 (95% CI: 1.1-3.2) vs. PCA 4.1 (95% CI: 3.4-4.8): P<0.002]. There were no clinically significant differences in mean daily pain scores, complications, or length of stay. Spinal opioid and continuous epidural analgesia decrease parenteral and oral opioid requirements compared with patient-controlled analgesia. The increased opioid usage in the patient-controlled analgesia group does not lead to clinically significant differences in pain scores, complications or length of stay. We conclude that all 3 methods of analgesia provide safe and effective pain relief. This study reinforces the need for collaboration between pediatric orthopaedic surgeons and anesthesiologists to effectively manage postoperative pain following posterior spinal fusion for adolescent idiopathic scoliosis. Level III-therapeutic study. Osteosarcoma, the most aggressive primary malignant bone tumor, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5-year overall survival (OS) is <30% for metastatic/recurrent cases. Plagued by genomic heterogeneity, immunosuppressive TME, and low immunogenicity, emerging immunotherapies lack robust large-scale clinical validation. We systematically analyzed 864 interventional osteosarcoma trials from Trialtrove (as of September 2025). Results showed trial numbers peaked at 54 in 2021, with 77.3% past (completed/terminated) and over 94% in phase I/II (only 3.6% phase III-IV). Geographically, the U.S. dominated (60.9%, focusing on immunotherapy/targeted therapy), while low- and middle-income countries (LMICs) accounted for <2%

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways. There is conflicting evidence for the optimal method of analgesia following posterior spinal fusion for adolescent idiopathic scoliosis. The primary objective of this study is to test which method of postoperative analgesia (continuous epidural, spinal opioids, or patient-controlled analgesia) is associated with reduced opioid requirements, pain scores, complications, and length of stay. This is a retrospective, multicenter study of the Shriners Children's International Pediatric Spine Database. Patients ages 13 to 19 years who had posterior spinal fusion with segmental spinal instrumentation for adolescent idiopathic scoliosis between January 01, 2011, and November 5, 2021, were eligible. Patients were divided into 3 cohorts based on the primary method of postoperative analgesia: continuous epidural (EPI), spinal opioid (SPI), or patient-controlled analgesia (PCA). We compared total parenteral and oral opioid usage, verbal numeric pain scores, complications, and the length of stay. A total of 2371 patients from 13 hospitals were included in the study. Total parenteral and oral opioid usage in the spinal and epidural groups was significantly lower compared with the patient-controlled analgesia group [OME/kg: SPI 1.7 (95% CI: 1.1-2.5) vs. EPI 1.9 (95% CI: 1.1-3.2) vs. PCA 4.1 (95% CI: 3.4-4.8): P<0.002]. There were no clinically significant differences in mean daily pain scores, complications, or length of stay. Spinal opioid and continuous epidural analgesia decrease parenteral and oral opioid requirements compared with patient-controlled analgesia. The increased opioid usage in the patient-controlled analgesia group does not lead to clinically significant differences in pain scores, complications or length of stay. We conclude that all 3 methods of analgesia provide safe and effective pain relief. This study reinforces the need for collaboration between pediatric orthopaedic surgeons and anesthesiologists to effectively manage postoperative pain following posterior spinal fusion for adolescent idiopathic scoliosis. Level III-therapeutic study. Osteosarcoma, the most aggressive primary malignant bone tumor, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5-year overall survival (OS) is <30% for metastatic/recurrent cases. Plagued by genomic heterogeneity, immunosuppressive TME, and low immunogenicity, emerging immunotherapies lack robust large-scale clinical validation. We systematically analyzed 864 interventional osteosarcoma trials from Trialtrove (as of September 2025). Results showed trial numbers peaked at 54 in 2021, with 77.3% past (completed/terminated) and over 94% in phase I/II (only 3.6% phase III-IV). Geographically, the U.S. dominated (60.9%, focusing on immunotherapy/targeted therapy), while low- and middle-income countries (LMICs) accounted for <2%

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways. There is conflicting evidence for the optimal method of analgesia following posterior spinal fusion for adolescent idiopathic scoliosis. The primary objective of this study is to test which method of postoperative analgesia (continuous epidural, spinal opioids, or patient-controlled analgesia) is associated with reduced opioid requirements, pain scores, complications, and length of stay. This is a retrospective, multicenter study of the Shriners Children's International Pediatric Spine Database. Patients ages 13 to 19 years who had posterior spinal fusion with segmental spinal instrumentation for adolescent idiopathic scoliosis between January 01, 2011, and November 5, 2021, were eligible. Patients were divided into 3 cohorts based on the primary method of postoperative analgesia: continuous epidural (EPI), spinal opioid (SPI), or patient-controlled analgesia (PCA). We compared total parenteral and oral opioid usage, verbal numeric pain scores, complications, and the length of stay. A total of 2371 patients from 13 hospitals were included in the study. Total parenteral and oral opioid usage in the spinal and epidural groups was significantly lower compared with the patient-controlled analgesia group [OME/kg: SPI 1.7 (95% CI: 1.1-2.5) vs. EPI 1.9 (95% CI: 1.1-3.2) vs. PCA 4.1 (95% CI: 3.4-4.8): P<0.002]. There were no clinically significant differences in mean daily pain scores, complications, or length of stay. Spinal opioid and continuous epidural analgesia decrease parenteral and oral opioid requirements compared with patient-controlled analgesia. The increased opioid usage in the patient-controlled analgesia group does not lead to clinically significant differences in pain scores, complications or length of stay. We conclude that all 3 methods of analgesia provide safe and effective pain relief. This study reinforces the need for collaboration between pediatric orthopaedic surgeons and anesthesiologists to effectively manage postoperative pain following posterior spinal fusion for adolescent idiopathic scoliosis. Level III-therapeutic study. Osteosarcoma, the most aggressive primary malignant bone tumor, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5-year overall survival (OS) is <30% for metastatic/recurrent cases. Plagued by genomic heterogeneity, immunosuppressive TME, and low immunogenicity, emerging immunotherapies lack robust large-scale clinical validation. We systematically analyzed 864 interventional osteosarcoma trials from Trialtrove (as of September 2025). Results showed trial numbers peaked at 54 in 2021, with 77.3% past (completed/terminated) and over 94% in phase I/II (only 3.6% phase III-IV). Geographically, the U.S. dominated (60.9%, focusing on immunotherapy/targeted therapy), while low- and middle-income countries (LMICs) accounted for <2%

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways. There is conflicting evidence for the optimal method of analgesia following posterior spinal fusion for adolescent idiopathic scoliosis. The primary objective of this study is to test which method of postoperative analgesia (continuous epidural, spinal opioids, or patient-controlled analgesia) is associated with reduced opioid requirements, pain scores, complications, and length of stay. This is a retrospective, multicenter study of the Shriners Children's International Pediatric Spine Database. Patients ages 13 to 19 years who had posterior spinal fusion with segmental spinal instrumentation for adolescent idiopathic scoliosis between January 01, 2011, and November 5, 2021, were eligible. Patients were divided into 3 cohorts based on the primary method of postoperative analgesia: continuous epidural (EPI), spinal opioid (SPI), or patient-controlled analgesia (PCA). We compared total parenteral and oral opioid usage, verbal numeric pain scores, complications, and the length of stay. A total of 2371 patients from 13 hospitals were included in the study. Total parenteral and oral opioid usage in the spinal and epidural groups was significantly lower compared with the patient-controlled analgesia group [OME/kg: SPI 1.7 (95% CI: 1.1-2.5) vs. EPI 1.9 (95% CI: 1.1-3.2) vs. PCA 4.1 (95% CI: 3.4-4.8): P<0.002]. There were no clinically significant differences in mean daily pain scores, complications, or length of stay. Spinal opioid and continuous epidural analgesia decrease parenteral and oral opioid requirements compared with patient-controlled analgesia. The increased opioid usage in the patient-controlled analgesia group does not lead to clinically significant differences in pain scores, complications or length of stay. We conclude that all 3 methods of analgesia provide safe and effective pain relief. This study reinforces the need for collaboration between pediatric orthopaedic surgeons and anesthesiologists to effectively manage postoperative pain following posterior spinal fusion for adolescent idiopathic scoliosis. Level III-therapeutic study. Osteosarcoma, the most aggressive primary malignant bone tumor, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5-year overall survival (OS) is <30% for metastatic/recurrent cases. Plagued by genomic heterogeneity, immunosuppressive TME, and low immunogenicity, emerging immunotherapies lack robust large-scale clinical validation. We systematically analyzed 864 interventional osteosarcoma trials from Trialtrove (as of September 2025). Results showed trial numbers peaked at 54 in 2021, with 77.3% past (completed/terminated) and over 94% in phase I/II (only 3.6% phase III-IV). Geographically, the U.S. dominated (60.9%, focusing on immunotherapy/targeted therapy), while low- and middle-income countries (LMICs) accounted for <2%

Despite therapeutic advances, multiple myeloma (MM) remains incurable due to the development of drug resistance by malignant plasma cells (PCs) and a severe immunosuppressive bone marrow (BM) microenvironment. Oncolytic virotherapy offers the dual benefit of tumor cell lysis and immune activation, but the efficacy of human viruses is often hampered by pre-existing antiviral immunity. Here, we demonstrated that bovine herpesvirus type 1 (BoHV-1), a virus that is nonpathogenic to humans, efficiently infected MM cells, inducing mitochondrial apoptosis and suppressing pro-survival programs, including MYC targets, oxidative phosphorylation, and the unfolded protein response. Infected tumor cells upregulated NK-activating ligands and downregulated MHC class I, enhancing susceptibility to NK-mediated cytotoxicity. In patientderived BM mononuclear cells (BMMCs), BoHV-1 selectively reduced malignant PCs and immunosuppressive myeloid subsets, while sparing lymphoid populations and hematopoietic progenitors. The infection promoted activation of CD8⁺ T cells, NK cells, and monocytes, driving a shift toward a pro-inflammatory M1-like polarization. Monocyte depletion in BMMCs attenuated the BoHV-1 anti-MM effect, confirming their functional contribution. This pronounced immune remodeling was accompanied by an inflammatory cytokine storm dominated by type I/II interferons and key innate immune mediators. Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment. Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor outcomes. The liposomal formulation of cytarabine and daunorubicin (CPX-351) improved complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates and overall survival (OS) compared with 'standard' induction (7+3) chemotherapy in a phase-III trial for patients aged 60-75 years. However, 7+3 dosing varies among trials and in clinical practice and it remains unknown whether CPX-351 is superior to 7+3 double-induction regimens including intermediate-dose cytarabine, as the one employed in the HOVON-SAKK-Nordic clinical trials. To address this question, we conducted a post-hoc analysis on t-AML/AML-MRC patients aged ≥60 years enrolled in three HOVON-SAKK-Nordic trials and defined a subset of patients that met the eligibility criteria of the CPX-351 trial and compared their outcomes with those of the CPX-351 arm using reconstructed survival data. CR/CRi rates were higher in the higher-intensity 7+3 cohort (67.8%) compared with CPX-351 (47.7%) with similar median OS between the two cohorts (10.1 months versus 8.9 months respectively, HR = 0.99; 95% CI 0.78-1.26, p=0.95). Thirty-day mortality (4.4% for higher-intensity 7+3 versus 5.9% for CPX-351) and adverse events, including febrile neutropenia (61% for higher-intensity 7+3 versus 68% for CPX-351), were comparable. The data suggest that obligatory double-induction may achieve outcomes similar to CPX-351 in these patients and provide a strong rationale for ongoing clinical trials comparing these regimens. Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways. There is conflicting evidence for the optimal method of analgesia following posterior spinal fusion for adolescent idiopathic scoliosis. The primary objective of this study is to test which method of postoperative analgesia (continuous epidural, spinal opioids, or patient-controlled analgesia) is associated with reduced opioid requirements, pain scores, complications, and length of stay. This is a retrospective, multicenter study of the Shriners Children's International Pediatric Spine Database. Patients ages 13 to 19 years who had posterior spinal fusion with segmental spinal instrumentation for adolescent idiopathic scoliosis between January 01, 2011, and November 5, 2021, were eligible. Patients were divided into 3 cohorts based on the primary method of postoperative analgesia: continuous epidural (EPI), spinal opioid (SPI), or patient-controlled analgesia (PCA). We compared total parenteral and oral opioid usage, verbal numeric pain scores, complications, and the length of stay. A total of 2371 patients from 13 hospitals were included in the study. Total parenteral and oral opioid usage in the spinal and epidural groups was significantly lower compared with the patient-controlled analgesia group [OME/kg: SPI 1.7 (95% CI: 1.1-2.5) vs. EPI 1.9 (95% CI: 1.1-3.2) vs. PCA 4.1 (95% CI: 3.4-4.8): P<0.002]. There were no clinically significant differences in mean daily pain scores, complications, or length of stay. Spinal opioid and continuous epidural analgesia decrease parenteral and oral opioid requirements compared with patient-controlled analgesia. The increased opioid usage in the patient-controlled analgesia group does not lead to clinically significant differences in pain scores, complications or length of stay. We conclude that all 3 methods of analgesia provide safe and effective pain relief. This study reinforces the need for collaboration between pediatric orthopaedic surgeons and anesthesiologists to effectively manage postoperative pain following posterior spinal fusion for adolescent idiopathic scoliosis. Level III-therapeutic study. Osteosarcoma, the most aggressive primary malignant bone tumor, has stagnant therapeutic outcomes despite decades of standard MAP chemotherapy and surgery; 5-year overall survival (OS) is <30% for metastatic/recurrent cases. Plagued by genomic heterogeneity, immunosuppressive TME, and low immunogenicity, emerging immunotherapies lack robust large-scale clinical validation. We systematically analyzed 864 interventional osteosarcoma trials from Trialtrove (as of September 2025). Results showed trial numbers peaked at 54 in 2021, with 77.3% past (completed/terminated) and over 94% in phase I/II (only 3.6% phase III-IV). Geographically, the U.S. dominated (60.9%, focusing on immunotherapy/targeted therapy), while low- and middle-income countries (LMICs) accounted for <2%

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Risk of fractures may be increased in individuals with iron deficiency, iron overload, and/or HFE hemochromatosis. To test this hypothesis, we followed 142,146 Danish general population individuals for a median of 11 years (range:0-41) after study enrolment for hospital and emergency room admissions with fractures. All individuals had blood samples drawn at study enrolment. We measured iron, transferrin saturation, and ferritin in 136,611, 136,555, and 37,990 individuals, respectively, while 132,499 individuals were genotyped for the HFE C282Y and H63D variants. We found a U-shaped relationship between fracture risk and concentrations of plasma iron and transferrin saturation when studying all individuals irrespective of genotype. When studied according to plasma ferritin, fracture risk was increased in individuals with low ferritin concentrations, while risk was not increased in individuals with high concentrations. When compared to non-carriers, HFE C282Y homozygotes had increased risk of any fracture (hazard ratio[HR]:1.38;95%CI:1.09-1.75;p=0.008), and risk was increased even in C282Y homozygotes with normal ferritin concentrations (HR:2.89;95%CI:1.50-5.56), which is important as these individuals would not usually be recommended for HFE genotyping according to clinical guidelines. When compared to non-carriers, risk of fracture of the hip and femur was increased in C282Y homozygotes (HR:1.78;95%CI:1.17-2.70;p=0.007) but surprisingly also in H63D homozygotes (HR:1.21;95%CI:1.00-1.47;p=0.04), C282Y heterozygotes (HR:1.10;95%CI:1.00-1.21;p=0.04), and C282Y/H63D compound heterozygotes (HR:1.23;95%CI:1.00-1.51;p=0.05). The markedly increased fracture risk in C282Y homozygotes with normal ferritin may challenge the presumption that systemic iron accumulation is the primary mechanism causing their increased fracture risk. Further studies are needed to examine whether phlebotomy reduces fracture risk. Epithelial lacrimal gland tumors are rare in children. This study presents a retrospective case series of 4 pediatric patients with primary lacrimal gland tumors of epithelial origin. A literature review was performed on previous cases of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Pediatric patients with PAs and ACCs treated at Le Bonheur Children's Medical Center and St. Jude Children's Research Hospital between June 2018 and May 2025 were identified using SNOMED and CPT codes. One case of PA and three cases of ACC were identified through imaging and confirmed by pathology and genetic studies. Mean age at presentation was 14 years, and common initial findings were proptosis (50%) and hypoglobus (75%). All patients underwent surgical excision, and ACC cases received adjuvant proton beam therapy (100%) and chemotherapy (33%). At a mean follow-up of 5 years, all remained disease-free. This study highlights the clinical presentation, treatment, and outcomes of pediatric lacrimal gland tumors of epithelial origin. Complete surgical resection was curative for PA, while ACC required multimodal therapy. The use of adjuvant therapy in the cases of ACC appears to reduce recurrence rates and emphasizes the efficacy of combined treatment in pediatric patients. We will report the efficacy and precautions for the systemic administration of immunosuppressants in refractory Mooren's ulcer. A 65-year-old woman with refractory Mooren's ulcer was referred to our hospital. Initial visual acuity was 0.01 (logMAR 2.0) in the right eye and hand motion vision in the left eye. The right eye showed anterior chamber hemorrhage and a circumscribed peripheral ulcer with corneal perforation. The patient underwent conjunctival excision and lamellar keratoplasty in the right eye. Systemic methylprednisolone and oral cyclosporine (CsA) were initiated, along with topical betamethasone and tacrolimus. Systemic medications were continued with gradual tapering. At 8.5 months, the patient developed varicella-zoster virus (VZV)-associated keratouveitis in the right eye. Systemic steroid administration was promptly discontinued, but CsA was continued at a reduced dose. Antiviral treatment led to prompt improvement. Oral CsA was discontinued after 16 months of treatment. The total cumulative dose of PSL was 1,803 mg, and CsA was 64,730 mg. No relapses occurred during 36 months of follow-up. Multidisciplinary care was required to manage systemic complications. The long-term systemic administration of steroids and immunosuppressants may be associated with sustained remission in a patient with refractory Mooren's ulcer with appropriate monitoring for various systemic conditions caused by immunosuppression. Muscle invasive bladder cancer (MIBC) is an aggressive disease with a high mortality rate. Radical cystectomy (RC) is the standard treatment for MIBC and selected non-muscle invasive bladder -cancer (NMIBC) cases. The NorCys-study (NCT04523038, NCT04537221 and NCT04523025) aims to validate biomarkers predicting RC outcomes. This report describes RC practice patterns across the Nordic countries. This prospective, multi-institutional study included bladder cancer patients undergoing RC with or without preoperative chemotherapy in all five Nordic countries from 5/2020 to 1/2025. Clinical and pathological data were collected prospectively into REDCap database and analysed using descriptive statistics, Wilcoxon rank sum and Pearson's Chi-squared tests. A total of 1,642 patients from 15 centres were enrolled. Of these, 35% (531) had clinical NMIBC (T1-Tis-Ta), and 65% (999) had cT2-4 disease. Preoperative chemotherapy was administered to 398/929 (43%) cT2-4 or node-positive patients. The most common neoadjuvant chemotherapy (NAC) regimens were gemcitabine - cisplatin (GC) (275/475 [58%]) and dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) (144/475 [30%]). Robot-assisted RC was the most common surgical approach administered in 886 of 1,472 (60%) cases, with variation between centres. Ileal conduit was the predominant diversion method in 1,375 out of 1,465 cases (94%). Median surgical time was 322 min, blood loss was 300 mL and hospital stay was 9 days. Final pathology demonstrated pT0 in 29%, ≥pT2 in 43% and lymph node metastases 203 (17%). This study reports current RC practices amongst Nordic countries. Patient cohorts did not differ between countries, and although the practices were generally similar, some differences were noted in chemotherapy regimens, the use of robotic-assisted surgery and rates of early RC. Strabismus is a major cause of ocular morbidity worldwide. Despite its prevalence, there is a limited understanding of its epidemiology and associated factors, particularly across diverse populations. This hospital-based, cross-sectional observational study included all patients diagnosed with strabismus at a tertiary care center between January 1 and December 31, 2023. A consecutive sampling method was used. Each patient underwent a comprehensive ophthalmic and strabismus examination, which included best-corrected visual acuity, cycloplegic refraction, and a detailed ocular history. Data were collected using a structured, interview-based proforma covering demographics, family history, medical history, and ocular history. The primary aim was to determine the distribution of strabismus types; secondary objectives included analyzing associated clinical and social factors. Among 75,917 new patients visiting the hospital, 1.5% (n = 1131) had strabismus. Exotropia slightly outnumbered esotropia (49.6% vs. 41.4%), with intermittent exotropia being the most common subtype. The highest hospital frequency was in children aged 1-6 years (37.4%) and the lowest in infants under 1 year (1.1%). Key associated factors included preterm birth, prolonged postnatal ICU stay, cesarean delivery, and cerebro-visual impairment. Refractive errors (20.2%) and amblyopia (13%) were common comorbidities. Strabismus remains a signifi

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction. Eosinophils are granulocytes that undergo extensive transcriptional and functional remodeling as they adapt to tissue-specific microenvironments, enabling them to perform context-dependent roles in both homeostasis and disease. The intestine, one of the most eosinophil-rich organs, exhibits profound spatial, temporal, and physiological heterogeneity that governs eosinophil adaptation. In this review, we present an integrative spatiotemporal and physiological framework that synthesizes current insights into how intestinal microenvironmental cues shape eosinophil identity and function. We first summarize regional specialization of eosinophils across the intestinal tract, followed by a systematic overview of the key factors that imprint eosinophil phenotype. We next discuss how these niche-driven adaptations enable eosinophils to regulate epithelial homeostasis, microbiota, and context-specific immune responses. We further review emerging clinical findings to highlight conserved and divergent aspects of eosinophil adaptation across intestinal diseases. A deeper understanding of the mechanisms underlying eosinophil adaptation in the gut may pave the way for targeted therapeutic strategies in intestinal health and disease. Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC. Moral distress (MD) is the negative feeling experienced by professionals who are unable to act according to what they consider correct. This can be influenced by personal, relational, or institutional factors. It can generate emotions such as anger, guilt, and hopelessness, affecting the quality of life of professionals and their clinical practices. Since its initial description in nursing regarding therapeutic futility, its study has expanded through validated scales that identify its frequency, intensity, and contexts. MD is associated with job dissatisfaction, professional burnout, and even leaving the profession. In pediatrics, it is strongly expressed in intensive care, neonatal care, and oncology. Unlike ethical dilemmas -where there is deliberation- in MD, the professional acts against their moral judgment, causing harm by rupturing moral identity. In pediatrics, complexity increases when the wishes of family members are incorporated into the specifications of care, without being completely certain about what the child would have preferred. The lack of institutional tools and resources exacerbates its impact, which was most evident during the COVID-19 pandemic. This article explores some known sources, how professionals are affected, and the often overlooked impact of the moral injury or moral imprint. The objective of exploring this topic has been to bring visibility to the phenomenon and to foster a discussion that allows us to reflect on strategies and the need to promote moral resilience among pediatric care professionals. Radiogenomics promises noninvasive tumor profiling; however, the extent to which imaging morphology reflects tumor lineage versus host-organ milieu remains unclear. This study aimed to quantify the relative influence of tumor type and anatomical environment on contrast-enhanced computed tomography (CT) radiomic phenotypes. A discovery cohort of 1,598 patients (10,485 lesions) and an external validation cohort of 2,440 patients (6,597 lesions) underwent portal-venous-phase CT. After manual segmentation, lesion-level radiomic features were standardized and embedded using t-distributed stochastic neighbor embedding. Bayesian-optimized agglomerative clustering defined morphology-based groups. Concordance with the primary tumor site (lineage) and anatomical environment was quantified using bootstrapped adjusted Rand indices (ARI); the silhouette score assessed clustering quality. Feature-class (shape, intensity, texture) and mask-erosion experiments probed mechanistic drivers. Six morphological clusters were identified in the discovery set (silhouette = 0.44). Morphology aligned more strongly with environment (mean ARI = 0.37) but poorly with lineage (mean ARI = 0.04; p < 0.010); this pattern held externally. In solid organ metastases, environment dominance was even stronger (mean ARI = 0.60 versus 0.05; p < 0.010). Intensity and texture drove the morphological association with anatomical environment (ARI = 0.64-0.56) more than shape (ARI = 0.06). When the periphery of the tumor was eroded, the same patterns were observed, implicat

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex

In an aging population, patients undergoing thyroidectomy and parathyroidectomy are at an increased risk of adverse outcomes; thus, measuring patient frailty is a key metric to assess risk. This study innovatively compares the utility of the Risk Analysis Index (RAI) with the 5-factor Modified Frailty Index (mFI-5) in predicting adverse postoperative outcomes. Retrospective cohort. US hospitals. Patients undergoing thyroidectomy or parathyroidectomy procedures were selected from the 2005 to 2020 NSQIP data set. RAI and mFI-5 frailty scores were calculated and stratified: non-frail (RAI: <21/mFI-5: <1), pre-frail (RAI: 21-30/mFI-5: 1), frail (RAI: 31-40/mFI-5: 2), and severely frail (RAI: 40+/mFI-5: 3-5) categories. Univariate and multivariate analyses were conducted, followed by receiver operating characteristic (ROC) curves, to evaluate the comparative discriminative thresholds of the indices. A cohort of 30,362 patients was identified with a median age of 56 years. Multivariate odds ratios showed that both indices were significant independent predictors of mortality (RAI: 15.508, P < .001; mFI-5: 10.713, P < .001), extended length of stay (eLOS) (RAI: 9.480, P < .001; mFI-5: 7.952, P < .001), non-home discharge (RAI: 15.897, P < .001; mFI-5: 9.346, P < .001), and Clavien-Dindo (CD) II complications (RAI: 7.130, P < .001; mFI-5: 3.760, P < .001). ROC analysis demonstrated significantly superior discrimination by the RAI for mortality (0.769 vs 0.650, P = .022), eLOS (0.712 vs 0.596, P < .001), non-home discharge (0.763 vs 0.639, P < .001), CD II (0.739 vs 0.566, P < .001), CD IIIb (0.644 vs 0.587, P = .002), CD IV (0.707 vs 0.622, P < .001), and organ/space infection (0.719 vs 0.519, P < .001). Both the RAI and mFI-5 frailty indices are comparable, significant predictors of adverse events in thyroidectomy/parathyroidectomy. The RAI demonstrated superior discrimination for predicting postoperative morbidity across most outcomes, indicating it may be a superior clinical tool for identifying high-risk patients. The RAI may better inform perioperative decision-making, patient counseling, and resource allocation. Extended length of stay (eLOS) after hip fracture surgery in elderly patients poses significant clinical and economic challenges. While traditional statistical models identify key predictors, they may miss complex variable interactions. This study compared logistic regression with machine learning (ML) algorithms to predict eLOS, emphasizing actionable factors within Enhanced Recovery After Surgery (ERAS) protocols. This retrospective cohort study analyzed 1137 patients aged ≥50 years who underwent hip arthroplasty or internal fixation for hip fracture (2019-2025). Extended LOS was defined as hospital stay ≥14 days based on median LOS of 13.8 days. Two prediction models were developed: preoperative (admission data only) and early in-hospital (including day-1 postoperative data). Multivariate logistic regression identified independent predictors, while nine ML algorithms were trained and validated using 10-fold cross-validation. Feature importance was assessed through SHAP analysis. Among 1137 patients, 500 (44.0%) experienced eLOS. Logistic regression identified male gender (odds ratio (OR) = 1.42, p = 0.01), delayed surgery >48 hours (OR = 2.31, p < 0.001), prolonged operation time (OR = 1.67, p = 0.02), and postoperative pneumonia (OR = 3.12, p < 0.001) as independent risk factors. Tranexamic acid (TXA) use was protective (OR = 0.65, p = 0.03). After 10-fold cross-validation, logistic regression and Support Vector Machine achieved area under the curve (AUC) = 0.76 (95% confidence interval (CI) 0.73-0.79), while XGBoost showed AUC = 0.72 (95% CI 0.69-0.75). SHAP (SHapley Additive exPlanations) analysis confirmed time-to-surgery, TXA use, and coagulation markers as key predictors across models. Both statistical and ML approaches identified delayed surgery and pneumonia as critical eLOS predictors, while ML revealed complex interactions involving coagulation dynamics and reinforced TXA's protective role. These findings support ML-augmented ERAS protocols targeting modifiable risk factors. External validation and clinical implementation studies are needed to confirm utility in routine practice. Each military service has independently developed austere resuscitative and surgical care (ARSC) team training courses that vary in use, content, duration, tactical exposure, and clinical emphasis. A 2020 Department of Defense Inspector General audit identified training deficits for ARSC teams. To close this gap, we developed ARSC curriculum standards for the Joint Force. A work group of Tri-Service appointed multidisciplinary subject matter experts (SMEs) reviewed available Role 2 and ARSC training courses to identify common curricular elements, best practices, and training gaps. Through an iterative process, these findings were incorporated into a standard curriculum organized into modules subdivided into terminal learning objectives (TLOs) and enabling learning objectives (ELOs), which were validated against Service doctrinal ARSC capability requirements. Curricula from 12 different courses were identified and reviewed. Most prepared teams for Counter Insurgency operations characterized by short holding times and rapid aeromedical evacuation. Eighty-two clinical and nonclinical common curricular best practices were identified. Only four courses had 50% or more of SME-recommended curricular elements. Identified curricular gaps included prolonged holding (0% of courses), definitive austere surgical care (0%), austere critical care (25%), simulated tactical exposure (25%), night operations familiarization (37.5%), and simulated operational environment (62.5%). Ten modules were created comprised of 20 TLOs and 259 ELOs incorporating curricular best practices and identified gaps. Military medicine is preparing surgical teams for the war just fought, not the future fight and lacks a joint standard for training Role 2/ARSC surgical teams, which is a risk to force and to mission. We close this gap by creating the first Joint Role 2 forward surgical/ARSC curriculum. To evaluate the accuracy of full-arch (FA) implant scan with a novel system (Nexus IOS®, Osteon Medical) using scan gauges (SGs), and to compare it with that of different conventional scan body (SB) systems that are currently available. A plaster model with 4 multi-unit-abutment analogs was prepared and inter-implant distances between its analogs were measured using a coordinate measuring machine (CMM), to obtain reference distances. An expert operator used an intraoral scanner (IOS) to capture scans with five different systems (Nexus IOS®, DESS®, Medentika®, IPD® and Elos®, n = 10 scans per group). These measurements were compared with the reference CMM-generated model to calculate inter-implant distance trueness. The study design addressed three questions: 1) Are there overall differences among the systems? 2) Are there overall differences among segments/points? and 3) For a given segment did systems perform differently? A statistical analysis was performed. Among the systems, Nexus IOS® system exhibited the highest trueness, followed by DESS®. Medentika® and IPD® showed slightly higher deviations and variability, indicating moderate performance. Elos® had the least trueness among the systems tested, with the highest median deviation and the widest overall spread, suggesting greater inconsistency in dimensional accuracy. Within the limitations of this in vitro study, the Nex